4-76739349-C-G

Position:

• chr4-76739349-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020859.4(SHROOM3):​c.1176C>G​(p.Tyr392*) variant causes a stop gained change involving the alteration of a non-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 Uncertain significance (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SHROOM3 NM_020859.4 stop_gained
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.664

Genes affected

SHROOM3 (HGNC:30422): (shroom family member 3) This gene encodes a PDZ-domain-containing protein that belongs to a family of Shroom-related proteins. This protein may be involved in regulating cell shape in certain tissues. A similar protein in mice is required for proper neurulation. [provided by RefSeq, Jan 2011]

SHROOM3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHROOM3	NM_020859.4	c.1176C>G	p.Tyr392*	stop_gained	5/11	ENST00000296043.7	NP_065910.3
SHROOM3-AS1	NR_187404.1	n.1044+3459G>C		intron_variant
SHROOM3-AS1	NR_187405.1	n.500+3459G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHROOM3	ENST00000296043.7	c.1176C>G	p.Tyr392*	stop_gained	5/11	1	NM_020859.4	ENSP00000296043.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 78

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Jul 01, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.55	D
Vest4		0.61
GERP RS		-4.4

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: rs761601802; hg19: chr4-77660502;