4-76739063-A-C

Position:

• chr4-76739063-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020859.4(SHROOM3):​c.890A>C​(p.Glu297Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SHROOM3 NM_020859.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.33

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-AS1 (HGNC:41265): (SHROOM3 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27234745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHROOM3	NM_020859.4	c.890A>C	p.Glu297Ala	missense_variant	5/11	ENST00000296043.7	NP_065910.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHROOM3	ENST00000296043.7	c.890A>C	p.Glu297Ala	missense_variant	5/11	1	NM_020859.4	ENSP00000296043	P1
SHROOM3-AS1	ENST00000666924.1	n.448+3745T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 77

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

The c.890A>C (p.E297A) alteration is located in exon 5 (coding exon 5) of the SHROOM3 gene. This alteration results from a A to C substitution at nucleotide position 890, causing the glutamic acid (E) at amino acid position 297 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T;.
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.7	M;.
MutationTaster	Benign	0.77	D
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-5.1	D;.
REVEL	Benign	0.13
Sift	Uncertain	0.0010	D;.
Sift4G	Uncertain	0.024	D;.
Polyphen		0.31	B;.
Vest4		0.14
MutPred		0.39		Loss of solvent accessibility (P = 0.0224);.;
MVP		0.26
MPC		0.95
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.47
gMVP		0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-77660216;