rs6126344

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020436.5(SALL4):c.1520T>G(p.Leu507Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 1,613,936 control chromosomes in the GnomAD database, including 99,606 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L507L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.30 ( 7711 hom., cov: 31)

Exomes 𝑓: 0.35 ( 91895 hom. )

Consequence

SALL4
NM_020436.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 2.27

Publications

37 publications found

Variant links:

Genes affected

SALL4 (HGNC:15924): (spalt like transcription factor 4) This gene encodes a zinc finger transcription factor thought to play a role in the development of abducens motor neurons. Defects in this gene are a cause of Duane-radial ray syndrome (DRRS). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

SALL4 Gene-Disease associations (from GenCC):

Duane-radial ray syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
Duane retraction syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
IVIC syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SALL4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.705168E-5).

BP6

Variant 20-51790963-A-C is Benign according to our data. Variant chr20-51790963-A-C is described in ClinVar as Benign. ClinVar VariationId is 261259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SALL4	NM_020436.5 link	c.1520T>G	p.Leu507Arg	missense_variant	Exon 2 of 4	ENST00000217086.9	NP_065169.1	Q9UJQ4-1
SALL4	XM_047440318.1 link	c.1214T>G	p.Leu405Arg	missense_variant	Exon 2 of 4		XP_047296274.1
SALL4	NM_001318031.2 link	c.1150+370T>G		intron_variant	Intron 2 of 3		NP_001304960.1	Q9UJQ4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SALL4	ENST00000217086.9 link	c.1520T>G	p.Leu507Arg	missense_variant	Exon 2 of 4	1	NM_020436.5	ENSP00000217086.4	Q9UJQ4-1
SALL4	ENST00000395997.3 link	c.1150+370T>G		intron_variant	Intron 2 of 3	1		ENSP00000379319.3	Q9UJQ4-2
SALL4	ENST00000371539.7 link	c.131-1822T>G		intron_variant	Intron 1 of 2	1		ENSP00000360594.3	Q6Y8G5

Frequencies

GnomAD3 genomes

AF:

0.301

AC:

45679

AN:

151968

Hom.:

7726

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.347

Gnomad AMR

AF:

0.339

Gnomad ASJ

AF:

0.425

Gnomad EAS

AF:

0.581

Gnomad SAS

AF:

0.433

Gnomad FIN

AF:

0.317

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.343

Gnomad OTH

AF:

0.362

GnomAD2 exomes

AF:

0.351

AC:

88212

AN:

251198

AF XY:

0.359

show subpopulations

Gnomad AFR exome

AF:

0.139

Gnomad AMR exome

AF:

0.287

Gnomad ASJ exome

AF:

0.412

Gnomad EAS exome

AF:

0.598

Gnomad FIN exome

AF:

0.317

Gnomad NFE exome

AF:

0.344

Gnomad OTH exome

AF:

0.359

GnomAD4 exome

AF:

0.350

AC:

511789

AN:

1461848

Hom.:

91895

Cov.:

AF XY:

0.353

AC XY:

256596

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.137

AC:

4600

AN:

33480

American (AMR)

AF:

0.291

AC:

12997

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.413

AC:

10803

AN:

26134

East Asian (EAS)

AF:

0.546

AC:

21662

AN:

39700

South Asian (SAS)

AF:

0.406

AC:

35019

AN:

86258

European-Finnish (FIN)

AF:

0.321

AC:

17131

AN:

53392

Middle Eastern (MID)

AF:

0.340

AC:

1961

AN:

5768

European-Non Finnish (NFE)

AF:

0.347

AC:

386079

AN:

1111998

Other (OTH)

AF:

0.357

AC:

21537

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

23878

47756

71635

95513

119391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12548

25096

37644

50192

62740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.300

AC:

45670

AN:

152088

Hom.:

7711

Cov.:

AF XY:

0.303

AC XY:

22536

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.147

AC:

6092

AN:

41518

American (AMR)

AF:

0.339

AC:

5174

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.425

AC:

1475

AN:

3472

East Asian (EAS)

AF:

0.581

AC:

2990

AN:

5148

South Asian (SAS)

AF:

0.431

AC:

2077

AN:

4822

European-Finnish (FIN)

AF:

0.317

AC:

3357

AN:

10584

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.343

AC:

23330

AN:

67966

Other (OTH)

AF:

0.359

AC:

756

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1582

3164

4747

6329

7911

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

474

948

1422

1896

2370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.334

Hom.:

25253

Bravo

AF:

0.298

TwinsUK

AF:

0.362

AC:

1344

ALSPAC

AF:

0.365

AC:

1407

ESP6500AA

AF:

0.150

AC:

660

ESP6500EA

AF:

0.344

AC:

2957

ExAC

AF:

0.350

AC:

42537

Asia WGS

AF:

0.497

AC:

1727

AN:

3478

EpiCase

AF:

0.356

EpiControl

AF:

0.361

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 04, 2017

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Duane-radial ray syndrome

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oculootoradial syndrome

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.13

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.48

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.48

MetaRNN

Benign

0.000057

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.1

PhyloP100

2.3

PrimateAI

Benign

0.31

PROVEAN

Benign

0.57

REVEL

Benign

0.059

Sift

Benign

0.59

Sift4G

Benign

0.47

Polyphen

0.024

Vest4

0.24

MPC

1.0

ClinPred

0.0043

GERP RS

1.9

Varity_R

0.068

gMVP

0.56

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over