NM_020436.5:c.410dupG

Variant names:

• chr20-51792072-G-GC
• rs879255537
• NM_020436.5:c.410dupG

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_020436.5(SALL4):​c.410dupG​(p.Gly138ArgfsTer43) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 30)
• Consequence: SALL4 NM_020436.5 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.17

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 Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 20-51792072-G-GC is Pathogenic according to our data. Variant chr20-51792072-G-GC is described in ClinVar as [Pathogenic]. Clinvar id is 218947.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SALL4	NM_020436.5	c.410dupG	p.Gly138ArgfsTer43	frameshift_variant	Exon 2 of 4	ENST00000217086.9	NP_065169.1
SALL4	NM_001318031.2	c.410dupG	p.Gly138ArgfsTer43	frameshift_variant	Exon 2 of 4		NP_001304960.1
SALL4	XM_047440318.1	c.104dupG	p.Gly36ArgfsTer43	frameshift_variant	Exon 2 of 4		XP_047296274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SALL4	ENST00000217086.9	c.410dupG	p.Gly138ArgfsTer43	frameshift_variant	Exon 2 of 4	1	NM_020436.5	ENSP00000217086.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 30

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Duane-radial ray syndrome Pathogenic:1

Mar 01, 2015

Laboratory of Human Genetics, Universidade de São Paulo

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: research

Okihiro syndrome without Duame anomaly being responsible for a severe case of foot defect in the proband. -

Computational scores

Source: dbNSFP v4.3

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: rs879255537; hg19: chr20-50408611;