rs765237474

Variant names:

• chr4-76738785-C-A
• rs765237474
• NM_020859.4:c.612C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-76738785-C-A
• chr4-76738785-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020859.4(SHROOM3):​c.612C>A​(p.Asn204Lys) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N204H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SHROOM3 NM_020859.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.464

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.067377985).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHROOM3	NM_020859.4	c.612C>A	p.Asn204Lys	missense_variant	Exon 5 of 11	ENST00000296043.7	NP_065910.3
SHROOM3-AS1	NR_187404.1	n.1044+4023G>T		intron_variant	Intron 3 of 3
SHROOM3-AS1	NR_187405.1	n.500+4023G>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHROOM3	ENST00000296043.7	c.612C>A	p.Asn204Lys	missense_variant	Exon 5 of 11	1	NM_020859.4	ENSP00000296043.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	17
DANN	Benign	0.90
DEOGEN2	Benign	0.33	T;.
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.067	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.7	D;.
REVEL	Benign	0.037
Sift	Uncertain	0.029	D;.
Sift4G	Uncertain	0.034	D;.
Polyphen		0.65	P;.
Vest4		0.12
MutPred		0.22		Gain of ubiquitination at N204 (P = 0.0029);.;
MVP		0.20
MPC		0.39
ClinPred		0.19	T
GERP RS		1.2
Varity_R		0.13
gMVP		0.097

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs765237474; hg19: chr4-77659938;