Variant rs199476308 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000404484.9(TPM1):c.47G>T(p.Ser16Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000782 in 1,535,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000072 ( 0 hom. )

Consequence

TPM1
ENST00000404484.9 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 1.70

Variant links:

Genes affected

TPM1 (HGNC:12010): (tropomyosin 1) This gene is a member of the tropomyosin family of highly conserved, widely distributed actin-binding proteins involved in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle cells. Tropomyosin is composed of two alpha-helical chains arranged as a coiled-coil. It is polymerized end to end along the two grooves of actin filaments and provides stability to the filaments. The encoded protein is one type of alpha helical chain that forms the predominant tropomyosin of striated muscle, where it also functions in association with the troponin complex to regulate the calcium-dependent interaction of actin and myosin during muscle contraction. In smooth muscle and non-muscle cells, alternatively spliced transcript variants encoding a range of isoforms have been described. Mutations in this gene are associated with type 3 familial hypertrophic cardiomyopathy and dilated cardiomyopathy 1Y. [provided by RefSeq, Jun 2022]

TPM1 links:

TPM1-AS (HGNC:53635): (TPM1 antisense RNA)

TPM1-AS links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2435976).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPM1	NM_001018005.2 linkuse as main transcript	c.240+4470G>T		intron_variant		ENST00000403994.9
TPM1-AS	NR_147233.2 linkuse as main transcript	n.621C>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPM1	ENST00000403994.9 linkuse as main transcript	c.240+4470G>T		intron_variant		1	NM_001018005.2	A1	P09493-1
TPM1-AS	ENST00000561241.1 linkuse as main transcript	n.766C>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000723

AC:

AN:

1383244

Hom.:

Cov.:

AF XY:

0.00000440

AC XY:

AN XY:

682424

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000226

Gnomad4 NFE exome

AF:

0.00000838

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not provided

Other:1

not provided, no classification provided

curation

Leiden Muscular Dystrophy (TPM1)

Apr 15, 2012

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.034

BayesDel_noAF

Benign

-0.19

Cadd

Benign

Dann

Benign

0.92

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.71

T;T;T;T;T;T

M_CAP

Pathogenic

0.66

MetaRNN

Benign

0.24

T;T;T;T;T;T

MetaSVM

Uncertain

0.22

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;N;N;N;N;N

PROVEAN

Benign

-0.83

N;N;.;N;N;N

REVEL

Uncertain

0.32

Sift

Benign

0.42

T;T;.;T;T;T

Sift4G

Benign

0.20

T;T;.;T;T;T

Polyphen

0.0040, 0.14

.;.;.;B;B;.

Vest4

0.41

MutPred

0.36

Loss of phosphorylation at S16 (P = 0.0134);Loss of phosphorylation at S16 (P = 0.0134);Loss of phosphorylation at S16 (P = 0.0134);Loss of phosphorylation at S16 (P = 0.0134);Loss of phosphorylation at S16 (P = 0.0134);Loss of phosphorylation at S16 (P = 0.0134);

MVP

0.64

ClinPred

0.10

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over