rs6013281

Positions:

• chr20-51791943-A-G
• chr20-51791943-A-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_020436.5(SALL4):​c.540T>C​(p.Asn180=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.996 in 1,614,230 control chromosomes in the GnomAD database, including 800,103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 1.0 (75670 hom., cov: 34)
  • Exomes 𝑓: 1.0 (724433 hom.)
• Consequence: SALL4 NM_020436.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.406

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 20-51791943-A-G is Benign according to our data. Variant chr20-51791943-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 261264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-51791943-A-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.406 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SALL4	NM_020436.5	c.540T>C	p.Asn180=	synonymous_variant	2/4	ENST00000217086.9
SALL4	NM_001318031.2	c.540T>C	p.Asn180=	synonymous_variant	2/4
SALL4	XM_047440318.1	c.234T>C	p.Asn78=	synonymous_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SALL4	ENST00000217086.9	c.540T>C	p.Asn180=	synonymous_variant	2/4	1	NM_020436.5	P1
SALL4	ENST00000395997.3	c.540T>C	p.Asn180=	synonymous_variant	2/4	1
SALL4	ENST00000371539.7	c.131-2802T>C		intron_variant		1
SALL4	ENST00000483130.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.997 AC: 151717 AN: 152220 Hom.: 75610 Cov.: 34

Gnomad AFR AF: 0.998

Gnomad AMI AF: 0.993

Gnomad AMR AF: 0.999

Gnomad ASJ AF: 0.994

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.995

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.995

Gnomad OTH AF: 0.996

GnomAD3 exomes AF: 0.997 AC: 250539 AN: 251400 Hom.: 124844 AF XY: 0.996 AC XY: 135372 AN XY: 135870

Gnomad AFR exome AF: 0.998

Gnomad AMR exome AF: 0.999

Gnomad ASJ exome AF: 0.994

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.995

Gnomad FIN exome AF: 0.999

Gnomad NFE exome AF: 0.995

Gnomad OTH exome AF: 0.996

GnomAD4 exome AF: 0.996 AC: 1455361 AN: 1461892 Hom.: 724433 Cov.: 93 AF XY: 0.995 AC XY: 723929 AN XY: 727246

Gnomad4 AFR exome AF: 0.997

Gnomad4 AMR exome AF: 0.999

Gnomad4 ASJ exome AF: 0.994

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.995

Gnomad4 FIN exome AF: 0.999

Gnomad4 NFE exome AF: 0.995

Gnomad4 OTH exome AF: 0.996

GnomAD4 genome AF: 0.997 AC: 151836 AN: 152338 Hom.: 75670 Cov.: 34 AF XY: 0.997 AC XY: 74268 AN XY: 74484

Gnomad4 AFR AF: 0.998

Gnomad4 AMR AF: 0.999

Gnomad4 ASJ AF: 0.994

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.995

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.995

Gnomad4 OTH AF: 0.996

Alfa AF: 0.995 Hom.: 31250

Bravo AF: 0.997

Asia WGS AF: 0.999 AC: 3473 AN: 3478

EpiCase AF: 0.995

EpiControl AF: 0.996

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 16, 2017	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Duane-radial ray syndrome Benign:2

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

not provided Benign:2

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

Oculootoradial syndrome;C1623209:Duane-radial ray syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 23, 2021

- -

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
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.46
DANN	Benign	0.42

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

Other links and lift over

dbSNP: rs6013281; hg19: chr20-50408482;