Variant rs61737142 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 12/20 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:3

Conservation

PhyloP100: 0.630

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE
SALL4	NM_020436.5 linkuse as main transcript	c.2182G>C	p.Ala728Pro	missense_variant	2/4	ENST00000217086.9
SALL4	XM_047440318.1 linkuse as main transcript	c.1876G>C	p.Ala626Pro	missense_variant	2/4
SALL4	NM_001318031.2 linkuse as main transcript	c.1150+1032G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SALL4	ENST00000217086.9 linkuse as main transcript	c.2182G>C	p.Ala728Pro	missense_variant	2/4	1	NM_020436.5	P1	Q9UJQ4-1
SALL4	ENST00000371539.7 linkuse as main transcript	c.131-1160G>C		intron_variant		1
SALL4	ENST00000395997.3 linkuse as main transcript	c.1150+1032G>C		intron_variant		1			Q9UJQ4-2

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

GnomAD3 exomes

AF:

0.00574

AC:

1442

AN:

251352

Hom.:

AF XY:

0.00434

AC XY:

590

AN XY:

135870

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 SAS exome

AF:

0.0000327

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

Gnomad4 AFR exome

AF:

0.0765

Gnomad4 AMR exome

AF:

0.00432

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000139

Gnomad4 OTH exome

AF:

0.00578

GnomAD4 genome

AF:

0.0219

AC:

3341

AN:

152272

Hom.:

139

Cov.:

AF XY:

0.0217

AC XY:

1618

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0763

Gnomad4 AMR

AF:

0.00797

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.0151

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Apr 08, 2016

- -

Duane-radial ray syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 26, 2018

- -

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

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

MutationTaster

Benign

0.73

D;D;D

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over