rs56095120

Variant names:

• chr22-31100540-T-A
• rs56095120
• NM_134269.3:c.2604-345T>A

Your query was ambiguous. Multiple possible variants found:

• chr22-31100540-T-A
• chr22-31100540-T-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_134269.3(SMTN):​c.2604-345T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0334 in 147,182 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.033 (112 hom., cov: 30)
• Consequence: SMTN NM_134269.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.605
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0334 (4920/147182) while in subpopulation EAS AF = 0.0439 (209/4766). AF 95% confidence interval is 0.0404. There are 112 homozygotes in GnomAd4. There are 2485 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 112 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.2604-345T>A		intron	N/A	NP_599031.1	P53814-5
	SMTN	NM_001382642.1		c.2886-345T>A		intron	N/A	NP_001369571.1
	SMTN	NM_001207017.1		c.2858+644T>A		intron	N/A	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.2604-345T>A		intron	N/A	ENSP00000329532.7	P53814-5
	SMTN	ENST00000347557.6	TSL:1	c.2603+644T>A		intron	N/A	ENSP00000328635.5	P53814-1
	SMTN	ENST00000619644.5	TSL:2	c.2858+644T>A		intron	N/A	ENSP00000484398.1	A0A087X1R1

Frequencies

GnomAD3 genomes AF: 0.0335 AC: 4927 AN: 147070 Hom.: 112 Cov.: 30

Gnomad AFR AF: 0.00708

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0306

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.0440

Gnomad SAS AF: 0.0233

Gnomad FIN AF: 0.0720

Gnomad MID AF: 0.0130

Gnomad NFE AF: 0.0417

Gnomad OTH AF: 0.0323

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0334 AC: 4920 AN: 147182 Hom.: 112 Cov.: 30 AF XY: 0.0346 AC XY: 2485 AN XY: 71746

African (AFR) AF: 0.00706 AC: 280 AN: 39682

American (AMR) AF: 0.0305 AC: 452 AN: 14802

Ashkenazi Jewish (ASJ) AF: 0.0542 AC: 186 AN: 3430

East Asian (EAS) AF: 0.0439 AC: 209 AN: 4766

South Asian (SAS) AF: 0.0227 AC: 101 AN: 4458

European-Finnish (FIN) AF: 0.0720 AC: 721 AN: 10016

Middle Eastern (MID) AF: 0.0105 AC: 3 AN: 286

European-Non Finnish (NFE) AF: 0.0417 AC: 2782 AN: 66788

Other (OTH) AF: 0.0315 AC: 65 AN: 2066

Alfa AF: 0.0356 Hom.: 20

Bravo AF: 0.0299

Asia WGS AF: 0.0250 AC: 88 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	18
DANN	Benign	0.86
PhyloP100		0.60
Mutation Taster		=100/0	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: rs56095120; hg19: chr22-31496526;