rs74315424

Positions:

• chr20-51790529-G-A

Variant summary

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

The NM_020436.5(SALL4):​c.1954C>T​(p.Gln652Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SALL4 NM_020436.5 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 10.0

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 20-51790529-G-A is Pathogenic according to our data. Variant chr20-51790529-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 3318.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SALL4	NM_020436.5	c.1954C>T	p.Gln652Ter	stop_gained	2/4	ENST00000217086.9	NP_065169.1
SALL4	XM_047440318.1	c.1648C>T	p.Gln550Ter	stop_gained	2/4		XP_047296274.1
SALL4	NM_001318031.2	c.1150+804C>T		intron_variant			NP_001304960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SALL4	ENST00000217086.9	c.1954C>T	p.Gln652Ter	stop_gained	2/4	1	NM_020436.5	ENSP00000217086	P1
SALL4	ENST00000371539.7	c.131-1388C>T		intron_variant		1		ENSP00000360594
SALL4	ENST00000395997.3	c.1150+804C>T		intron_variant		1		ENSP00000379319

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

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

literature only

OMIM

Jul 01, 2003

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.60	D
BayesDel_noAF	Pathogenic	0.62
CADD	Pathogenic	41
DANN	Uncertain	1.0
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.96
FATHMM_MKL	Uncertain	0.95	D
MutationTaster	Benign	1.0	A;A;A
Vest4		0.89
GERP RS		5.6

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: rs74315424; hg19: chr20-50407068; COSMIC: COSV99409404; COSMIC: COSV99409404;