rs6126344

Positions:

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as 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

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=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 id is 261259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-51790963-A-C is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
SALL4	NM_020436.5 linkuse as main transcript	c.1520T>G	p.Leu507Arg	missense_variant	2/4	ENST00000217086.9	NP_065169.1	Q9UJQ4-1
SALL4	XM_047440318.1 linkuse as main transcript	c.1214T>G	p.Leu405Arg	missense_variant	2/4		XP_047296274.1
SALL4	NM_001318031.2 linkuse as main transcript	c.1150+370T>G		intron_variant			NP_001304960.1	Q9UJQ4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SALL4	ENST00000217086.9 linkuse as main transcript	c.1520T>G	p.Leu507Arg	missense_variant	2/4	1	NM_020436.5	ENSP00000217086.4	Q9UJQ4-1
SALL4	ENST00000395997.3 linkuse as main transcript	c.1150+370T>G		intron_variant		1		ENSP00000379319.3	Q9UJQ4-2
SALL4	ENST00000371539.7 linkuse as main transcript	c.131-1822T>G		intron_variant		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

GnomAD3 exomes

AF:

0.351

AC:

88212

AN:

251198

Hom.:

16798

AF XY:

0.359

AC XY:

48748

AN XY:

135848

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 SAS exome

AF:

0.416

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

Gnomad4 AFR exome

AF:

0.137

Gnomad4 AMR exome

AF:

0.291

Gnomad4 ASJ exome

AF:

0.413

Gnomad4 EAS exome

AF:

0.546

Gnomad4 SAS exome

AF:

0.406

Gnomad4 FIN exome

AF:

0.321

Gnomad4 NFE exome

AF:

0.347

Gnomad4 OTH exome

AF:

0.357

GnomAD4 genome

AF:

0.300

AC:

45670

AN:

152088

Hom.:

7711

Cov.:

AF XY:

0.303

AC XY:

22536

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.147

Gnomad4 AMR

AF:

0.339

Gnomad4 ASJ

AF:

0.425

Gnomad4 EAS

AF:

0.581

Gnomad4 SAS

AF:

0.431

Gnomad4 FIN

AF:

0.317

Gnomad4 NFE

AF:

0.343

Gnomad4 OTH

AF:

0.359

Alfa

AF:

0.346

Hom.:

9512

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

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 04, 2017	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Duane-radial ray syndrome

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Oculootoradial syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

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

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

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

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