rs748966600

Variant names:

• chr22-31083263-C-A
• rs748966600
• NM_134269.3:c.5C>A

Your query was ambiguous. Multiple possible variants found:

• chr22-31083263-C-A
• chr22-31083263-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_134269.3(SMTN):​c.5C>A​(p.Ala2Glu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SMTN NM_134269.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52

Genes affected

SMTN (HGNC:11126): (smoothelin) This gene encodes a structural protein that is found exclusively in contractile smooth muscle cells. It associates with stress fibers and constitutes part of the cytoskeleton. This gene is localized to chromosome 22q12.3, distal to the TUPLE1 locus and outside the DiGeorge syndrome deletion. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2011]

ENSG00000273387 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM1: In a modified_residue N-acetylalanine (size 0) in uniprot entity SMTN_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2869398).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMTN	NM_134269.3	c.5C>A	p.Ala2Glu	missense_variant	Exon 2 of 21	ENST00000333137.12	NP_599031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMTN	ENST00000333137.12	c.5C>A	p.Ala2Glu	missense_variant	Exon 2 of 21	1	NM_134269.3	ENSP00000329532.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.056	.;T;.;.;.;T;.;.;.
Eigen	Benign	-0.025
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.80	T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.29	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	.;.;.;.;N;N;N;.;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.7	D;D;D;D;N;N;N;.;.
REVEL	Benign	0.13
Sift	Uncertain	0.0040	D;D;D;D;D;D;D;.;.
Sift4G	Pathogenic	0.0	D;D;D;D;T;T;T;D;D
Polyphen		0.99, 1.0	.;.;.;.;.;D;D;.;.
Vest4		0.42, 0.47, 0.39, 0.61
MutPred		0.14		.;Gain of solvent accessibility (P = 0.1185);.;.;Gain of solvent accessibility (P = 0.1185);Gain of solvent accessibility (P = 0.1185);Gain of solvent accessibility (P = 0.1185);Gain of solvent accessibility (P = 0.1185);.;
MVP		0.082
MPC		0.64
ClinPred		0.91	D
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.30
gMVP		0.51

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: rs748966600; hg19: chr22-31479249;