rs6091375

Variant names:

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.2392A>C(p.Ile798Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0544 in 1,614,114 control chromosomes in the GnomAD database, including 2,966 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I798V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.077 ( 636 hom., cov: 32)

Exomes 𝑓: 0.052 ( 2330 hom. )

Consequence

SALL4
NM_020436.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.895

Publications

14 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=0.0021042824).

BP6

Variant 20-51790091-T-G is Benign according to our data. Variant chr20-51790091-T-G is described in ClinVar as Benign. ClinVar VariationId is 261262.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
SALL4	NM_020436.5 link	c.2392A>C	p.Ile798Leu	missense_variant	Exon 2 of 4	ENST00000217086.9	NP_065169.1
SALL4	XM_047440318.1 link	c.2086A>C	p.Ile696Leu	missense_variant	Exon 2 of 4		XP_047296274.1
SALL4	NM_001318031.2 link	c.1151-950A>C		intron_variant	Intron 2 of 3		NP_001304960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SALL4	ENST00000217086.9 link	c.2392A>C	p.Ile798Leu	missense_variant	Exon 2 of 4	1	NM_020436.5	ENSP00000217086.4
SALL4	ENST00000395997.3 link	c.1151-950A>C		intron_variant	Intron 2 of 3	1		ENSP00000379319.3
SALL4	ENST00000371539.7 link	c.131-950A>C		intron_variant	Intron 1 of 2	1		ENSP00000360594.3

Frequencies

GnomAD3 genomes

AF:

0.0768

AC:

11680

AN:

152120

Hom.:

632

Cov.:

show subpopulations

Gnomad AFR

AF:

0.155

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.0470

Gnomad ASJ

AF:

0.0510

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0249

Gnomad FIN

AF:

0.0278

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0552

Gnomad OTH

AF:

0.0659

GnomAD2 exomes

AF:

0.0476

AC:

11968

AN:

251482

AF XY:

0.0455

show subpopulations

Gnomad AFR exome

AF:

0.162

Gnomad AMR exome

AF:

0.0311

Gnomad ASJ exome

AF:

0.0518

Gnomad EAS exome

AF:

0.00179

Gnomad FIN exome

AF:

0.0262

Gnomad NFE exome

AF:

0.0537

Gnomad OTH exome

AF:

0.0508

GnomAD4 exome

AF:

0.0520

AC:

76044

AN:

1461876

Hom.:

2330

Cov.:

AF XY:

0.0509

AC XY:

37040

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.164

AC:

5499

AN:

33480

American (AMR)

AF:

0.0338

AC:

1512

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0520

AC:

1358

AN:

26136

East Asian (EAS)

AF:

0.000932

AC:

AN:

39700

South Asian (SAS)

AF:

0.0255

AC:

2197

AN:

86258

European-Finnish (FIN)

AF:

0.0274

AC:

1466

AN:

53410

Middle Eastern (MID)

AF:

0.0591

AC:

341

AN:

5768

European-Non Finnish (NFE)

AF:

0.0541

AC:

60178

AN:

1112004

Other (OTH)

AF:

0.0572

AC:

3456

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

4686

9372

14057

18743

23429

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2278

4556

6834

9112

11390

<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:

0.0769

AC:

11706

AN:

152238

Hom.:

636

Cov.:

AF XY:

0.0740

AC XY:

5506

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.155

AC:

6433

AN:

41524

American (AMR)

AF:

0.0470

AC:

718

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0510

AC:

177

AN:

3468

East Asian (EAS)

AF:

0.00116

AC:

AN:

5176

South Asian (SAS)

AF:

0.0247

AC:

119

AN:

4824

European-Finnish (FIN)

AF:

0.0278

AC:

295

AN:

10616

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0552

AC:

3754

AN:

68018

Other (OTH)

AF:

0.0652

AC:

138

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

533

1066

1599

2132

2665

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

134

268

402

536

670

<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:

0.0619

Hom.:

779

Bravo

AF:

0.0820

TwinsUK

AF:

0.0526

AC:

195

ALSPAC

AF:

0.0550

AC:

212

ESP6500AA

AF:

0.158

AC:

696

ESP6500EA

AF:

0.0579

AC:

498

ExAC

AF:

0.0510

AC:

6188

Asia WGS

AF:

0.0210

AC:

AN:

3478

EpiCase

AF:

0.0586

EpiControl

AF:

0.0555

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Duane-radial ray syndrome

Benign:1

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

0.099

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.12

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.11

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.14

MetaRNN

Benign

0.0021

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.6

PhyloP100

-0.90

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.14

REVEL

Benign

0.018

Sift

Benign

0.67

Sift4G

Benign

0.96

Polyphen

0.0010

Vest4

0.040

MPC

0.33

ClinPred

0.0033

GERP RS

-5.1

Varity_R

0.060

gMVP

0.13

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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