rs61737142

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.2182G>C(p.Ala728Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0041 in 1,614,154 control chromosomes in the GnomAD database, including 254 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 139 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 115 hom. )

Consequence

SALL4
NM_020436.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.630

Publications

1 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=0.0027288496).

BP6

Variant 20-51790301-C-G is Benign according to our data. Variant chr20-51790301-C-G is described in ClinVar as Benign. ClinVar VariationId is 287110.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SALL4	NM_020436.5 link	c.2182G>C	p.Ala728Pro	missense_variant	Exon 2 of 4	ENST00000217086.9	NP_065169.1	Q9UJQ4-1
SALL4	XM_047440318.1 link	c.1876G>C	p.Ala626Pro	missense_variant	Exon 2 of 4		XP_047296274.1
SALL4	NM_001318031.2 link	c.1150+1032G>C		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.2182G>C	p.Ala728Pro	missense_variant	Exon 2 of 4	1	NM_020436.5	ENSP00000217086.4	Q9UJQ4-1
SALL4	ENST00000395997.3 link	c.1150+1032G>C		intron_variant	Intron 2 of 3	1		ENSP00000379319.3	Q9UJQ4-2
SALL4	ENST00000371539.7 link	c.131-1160G>C		intron_variant	Intron 1 of 2	1		ENSP00000360594.3	Q6Y8G5

Frequencies

GnomAD3 genomes

AF:

0.0219

AC:

3331

AN:

152154

Hom.:

138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0763

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00798

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.0148

GnomAD2 exomes

AF:

0.00574

AC:

1442

AN:

251352

AF XY:

0.00434

show subpopulations

Gnomad AFR exome

AF:

0.0783

Gnomad AMR exome

AF:

0.00379

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000220

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00224

AC:

3279

AN:

1461882

Hom.:

115

Cov.:

AF XY:

0.00198

AC XY:

1443

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.0765

AC:

2560

AN:

33480

American (AMR)

AF:

0.00432

AC:

193

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00295

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000139

AC:

155

AN:

1112012

Other (OTH)

AF:

0.00578

AC:

349

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

234

467

701

934

1168

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<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:

0.0219

AC:

3341

AN:

152272

Hom.:

139

Cov.:

AF XY:

0.0217

AC XY:

1618

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0763

AC:

3169

AN:

41540

American (AMR)

AF:

0.00797

AC:

122

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000220

AC:

AN:

68028

Other (OTH)

AF:

0.0151

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

168

336

504

672

840

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.00320

Hom.:

Bravo

AF:

0.0249

ESP6500AA

AF:

0.0767

AC:

338

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00719

AC:

873

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 26, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Apr 08, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Duane-radial ray syndrome

Benign:1

Jan 22, 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

0.11

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.55

MetaRNN

Benign

0.0027

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

2.9

PhyloP100

0.63

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.0

REVEL

Benign

0.10

Sift

Uncertain

0.0040

Sift4G

Benign

0.15

Polyphen

0.028

Vest4

0.67

MVP

0.20

MPC

0.88

ClinPred

0.046

GERP RS

3.6

Varity_R

0.25

gMVP

0.31

Mutation Taster

=92/8

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