rs879255537

chr20-51792072-G-GC

Variant summary

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

The NM_020436.5(SALL4):c.410_411insG(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). Synonymous variant affecting the same amino acid position (i.e. G137G) has been classified as Likely benign. 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/exons	MANE	UniProt
SALL4	NM_020436.5	c.410_411insG	p.Gly138ArgfsTer43	frameshift_variant	2/4	ENST00000217086.9
SALL4	NM_001318031.2	c.410_411insG	p.Gly138ArgfsTer43	frameshift_variant	2/4
SALL4	XM_047440318.1	c.104_105insG	p.Gly36ArgfsTer43	frameshift_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SALL4	ENST00000217086.9	c.410_411insG	p.Gly138ArgfsTer43	frameshift_variant	2/4	1	NM_020436.5	P1

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

Pathogenic, no assertion criteria provided

research

Laboratory of Human Genetics, Universidade de São Paulo

Mar 01, 2015

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;