chr22-31083296-C-T

Variant names:

• chr22-31083296-C-T
• rs150120759
• NM_134269.3:c.38C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_134269.3(SMTN):​c.38C>T​(p.Ala13Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000835 in 1,577,332 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00076 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00084 (3 hom.)
• Consequence: SMTN NM_134269.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.33
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02765435).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_134269.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMTN	NM_134269.3	MANE Select	c.38C>T	p.Ala13Val	missense	Exon 2 of 21	NP_599031.1	P53814-5
	SMTN	NM_001382642.1		c.320C>T	p.Ala107Val	missense	Exon 4 of 23	NP_001369571.1
	SMTN	NM_001207017.1		c.200C>T	p.Ala67Val	missense	Exon 2 of 21	NP_001193946.1	A0A087X1R1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMTN	ENST00000333137.12	TSL:1 MANE Select	c.38C>T	p.Ala13Val	missense	Exon 2 of 21	ENSP00000329532.7	P53814-5
	SMTN	ENST00000347557.6	TSL:1	c.38C>T	p.Ala13Val	missense	Exon 2 of 20	ENSP00000328635.5	P53814-1
	SMTN	ENST00000619644.5	TSL:2	c.200C>T	p.Ala67Val	missense	Exon 2 of 21	ENSP00000484398.1	A0A087X1R1

Frequencies

GnomAD3 genomes AF: 0.000762 AC: 116 AN: 152172 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00146

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000579 AC: 115 AN: 198490 AF XY: 0.000594

Gnomad AFR exome AF: 0.000387

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000173

Gnomad NFE exome AF: 0.00107

Gnomad OTH exome AF: 0.000404

GnomAD4 exome AF: 0.000843 AC: 1201 AN: 1425042 Hom.: 3 Cov.: 31 AF XY: 0.000868 AC XY: 612 AN XY: 705180

African (AFR) AF: 0.000182 AC: 6 AN: 33030

American (AMR) AF: 0.000268 AC: 10 AN: 37374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24810

East Asian (EAS) AF: 0.00 AC: 0 AN: 38696

South Asian (SAS) AF: 0.00 AC: 0 AN: 80664

European-Finnish (FIN) AF: 0.000156 AC: 8 AN: 51378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4158

European-Non Finnish (NFE) AF: 0.00104 AC: 1140 AN: 1095886

Other (OTH) AF: 0.000627 AC: 37 AN: 59046

GnomAD4 genome AF: 0.000762 AC: 116 AN: 152290 Hom.: 0 Cov.: 33 AF XY: 0.000766 AC XY: 57 AN XY: 74456

African (AFR) AF: 0.000217 AC: 9 AN: 41554

American (AMR) AF: 0.000458 AC: 7 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00146 AC: 99 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000797 Hom.: 0

Bravo AF: 0.000740

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.000411 AC: 49

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.068	T
Eigen	Benign	0.059
Eigen_PC	Benign	0.019
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.3
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.11
Sift	Uncertain	0.0090	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.49
MVP		0.043
MPC		0.67
ClinPred		0.057	T
GERP RS		2.1
PromoterAI		0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.13
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs150120759; hg19: chr22-31479282;