20-51790623-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020436.5(SALL4):c.1860A>G(p.Thr620Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 1,613,806 control chromosomes in the GnomAD database, including 101,222 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8331 hom., cov: 32)

Exomes 𝑓: 0.35 ( 92891 hom. )

Consequence

SALL4
NM_020436.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.84

Publications

24 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 20-51790623-T-C is Benign according to our data. Variant chr20-51790623-T-C is described in ClinVar as Benign. ClinVar VariationId is 261260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.84 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
SALL4	NM_020436.5 link	c.1860A>G	p.Thr620Thr	synonymous_variant	Exon 2 of 4	ENST00000217086.9	NP_065169.1
SALL4	XM_047440318.1 link	c.1554A>G	p.Thr518Thr	synonymous_variant	Exon 2 of 4		XP_047296274.1
SALL4	NM_001318031.2 link	c.1150+710A>G		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.1860A>G	p.Thr620Thr	synonymous_variant	Exon 2 of 4	1	NM_020436.5	ENSP00000217086.4
SALL4	ENST00000395997.3 link	c.1150+710A>G		intron_variant	Intron 2 of 3	1		ENSP00000379319.3
SALL4	ENST00000371539.7 link	c.131-1482A>G		intron_variant	Intron 1 of 2	1		ENSP00000360594.3

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

48852

AN:

151872

Hom.:

8341

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.349

Gnomad AMR

AF:

0.350

Gnomad ASJ

AF:

0.425

Gnomad EAS

AF:

0.587

Gnomad SAS

AF:

0.436

Gnomad FIN

AF:

0.317

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.344

Gnomad OTH

AF:

0.377

GnomAD2 exomes

AF:

0.357

AC:

89799

AN:

251362

AF XY:

0.364

show subpopulations

Gnomad AFR exome

AF:

0.208

Gnomad AMR exome

AF:

0.292

Gnomad ASJ exome

AF:

0.412

Gnomad EAS exome

AF:

0.600

Gnomad FIN exome

AF:

0.317

Gnomad NFE exome

AF:

0.345

Gnomad OTH exome

AF:

0.363

GnomAD4 exome

AF:

0.353

AC:

515945

AN:

1461818

Hom.:

92891

Cov.:

AF XY:

0.355

AC XY:

258514

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.207

AC:

6933

AN:

33480

American (AMR)

AF:

0.296

AC:

13244

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.413

AC:

10804

AN:

26136

East Asian (EAS)

AF:

0.546

AC:

21693

AN:

39700

South Asian (SAS)

AF:

0.408

AC:

35208

AN:

86258

European-Finnish (FIN)

AF:

0.321

AC:

17137

AN:

53398

Middle Eastern (MID)

AF:

0.343

AC:

1976

AN:

5768

European-Non Finnish (NFE)

AF:

0.348

AC:

387049

AN:

1111962

Other (OTH)

AF:

0.363

AC:

21901

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

24760

49521

74281

99042

123802

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12610

25220

37830

50440

63050

<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:

0.321

AC:

48852

AN:

151988

Hom.:

8331

Cov.:

AF XY:

0.324

AC XY:

24086

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.217

AC:

8990

AN:

41476

American (AMR)

AF:

0.350

AC:

5339

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.425

AC:

1473

AN:

3466

East Asian (EAS)

AF:

0.587

AC:

3019

AN:

5144

South Asian (SAS)

AF:

0.433

AC:

2087

AN:

4816

European-Finnish (FIN)

AF:

0.317

AC:

3344

AN:

10550

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.344

AC:

23390

AN:

67966

Other (OTH)

AF:

0.374

AC:

788

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1660

3320

4981

6641

8301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

498

996

1494

1992

2490

<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:

0.325

Hom.:

4479

Bravo

AF:

0.321

Asia WGS

AF:

0.510

AC:

1772

AN:

3478

EpiCase

AF:

0.357

EpiControl

AF:

0.362

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Apr 08, 2016

Eurofins Ntd Llc (ga)

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

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

Duane-radial ray syndrome

Benign:2

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

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

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.037

(source)

DANN

Benign

0.34

PhyloP100

-1.8

Mutation Taster

=99/1

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