chr20-51788963-C-G

Variant names:

• chr20-51788963-C-G
• rs17802735
• NM_020436.5:c.2640G>C

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.2640G>C​(p.Ser880Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,614,150 control chromosomes in the GnomAD database, including 12,275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.088 (811 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11464 hom.)
• Consequence: SALL4 NM_020436.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -5.38

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=-0.78).
• BP6: Variant 20-51788963-C-G is Benign according to our data. Variant chr20-51788963-C-G is described in ClinVar as [Benign]. Clinvar id is 261263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-51788963-C-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-5.38 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SALL4	NM_020436.5	c.2640G>C	p.Ser880Ser	synonymous_variant	Exon 3 of 4	ENST00000217086.9	NP_065169.1
SALL4	NM_001318031.2	c.1329G>C	p.Ser443Ser	synonymous_variant	Exon 3 of 4		NP_001304960.1
SALL4	XM_047440318.1	c.2334G>C	p.Ser778Ser	synonymous_variant	Exon 3 of 4		XP_047296274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SALL4	ENST00000217086.9	c.2640G>C	p.Ser880Ser	synonymous_variant	Exon 3 of 4	1	NM_020436.5	ENSP00000217086.4
SALL4	ENST00000395997.3	c.1329G>C	p.Ser443Ser	synonymous_variant	Exon 3 of 4	1		ENSP00000379319.3
SALL4	ENST00000371539.7	c.309G>C	p.Ser103Ser	synonymous_variant	Exon 2 of 3	1		ENSP00000360594.3

Frequencies

GnomAD3 genomes AF: 0.0877 AC: 13341 AN: 152168 Hom.: 811 Cov.: 32

Gnomad AFR AF: 0.0227

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.0809

Gnomad ASJ AF: 0.0698

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0697

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.0740

GnomAD3 exomes AF: 0.0916 AC: 23021 AN: 251444 Hom.: 1317 AF XY: 0.0945 AC XY: 12842 AN XY: 135906

Gnomad AFR exome AF: 0.0223

Gnomad AMR exome AF: 0.0481

Gnomad ASJ exome AF: 0.0750

Gnomad EAS exome AF: 0.000598

Gnomad SAS exome AF: 0.0772

Gnomad FIN exome AF: 0.108

Gnomad NFE exome AF: 0.131

Gnomad OTH exome AF: 0.0945

GnomAD4 exome AF: 0.120 AC: 175852 AN: 1461864 Hom.: 11464 Cov.: 32 AF XY: 0.119 AC XY: 86581 AN XY: 727234

Gnomad4 AFR exome AF: 0.0184

Gnomad4 AMR exome AF: 0.0515

Gnomad4 ASJ exome AF: 0.0734

Gnomad4 EAS exome AF: 0.000353

Gnomad4 SAS exome AF: 0.0770

Gnomad4 FIN exome AF: 0.108

Gnomad4 NFE exome AF: 0.137

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.0876 AC: 13339 AN: 152286 Hom.: 811 Cov.: 32 AF XY: 0.0863 AC XY: 6426 AN XY: 74466

Gnomad4 AFR AF: 0.0226

Gnomad4 AMR AF: 0.0808

Gnomad4 ASJ AF: 0.0698

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0698

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.0733

Alfa AF: 0.0916 Hom.: 294

Bravo AF: 0.0812

EpiCase AF: 0.129

EpiControl AF: 0.126

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

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

- -

-

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

Significance: Benign

Review Status: no assertion criteria provided

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

- -

Duane-radial ray syndrome Benign:1

Feb 03, 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
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.011
DANN	Benign	0.55

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: rs17802735; hg19: chr20-50405502;