Variant chr15-63056897-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001018005.2(TPM1):c.241-88G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,580,308 control chromosomes in the GnomAD database, including 246,113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 21038 hom., cov: 32)

Exomes 𝑓: 0.56 ( 225075 hom. )

Consequence

TPM1
NM_001018005.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.381

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 15-63056897-G-A is Benign according to our data. Variant chr15-63056897-G-A is described in ClinVar as [Benign]. Clinvar id is 1267396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63056897-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPM1	NM_001018005.2 linkuse as main transcript	c.241-88G>A		intron_variant		ENST00000403994.9	NP_001018005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPM1	ENST00000403994.9 linkuse as main transcript	c.241-88G>A		intron_variant		1	NM_001018005.2	ENSP00000385107	A1	P09493-1

Frequencies

GnomAD3 genomes

AF:

0.520

AC:

78981

AN:

151988

Hom.:

21046

Cov.:

show subpopulations

Gnomad AFR

AF:

0.423

Gnomad AMI

AF:

0.671

Gnomad AMR

AF:

0.458

Gnomad ASJ

AF:

0.565

Gnomad EAS

AF:

0.557

Gnomad SAS

AF:

0.483

Gnomad FIN

AF:

0.601

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.575

Gnomad OTH

AF:

0.518

GnomAD4 exome

AF:

0.559

AC:

798181

AN:

1428202

Hom.:

225075

Cov.:

AF XY:

0.557

AC XY:

397076

AN XY:

712530

show subpopulations

Gnomad4 AFR exome

AF:

0.421

Gnomad4 AMR exome

AF:

0.395

Gnomad4 ASJ exome

AF:

0.582

Gnomad4 EAS exome

AF:

0.563

Gnomad4 SAS exome

AF:

0.476

Gnomad4 FIN exome

AF:

0.610

Gnomad4 NFE exome

AF:

0.574

Gnomad4 OTH exome

AF:

0.552

GnomAD4 genome

AF:

0.519

AC:

78983

AN:

152106

Hom.:

21038

Cov.:

AF XY:

0.520

AC XY:

38640

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.423

Gnomad4 AMR

AF:

0.458

Gnomad4 ASJ

AF:

0.565

Gnomad4 EAS

AF:

0.558

Gnomad4 SAS

AF:

0.483

Gnomad4 FIN

AF:

0.601

Gnomad4 NFE

AF:

0.575

Gnomad4 OTH

AF:

0.513

Alfa

AF:

0.560

Hom.:

27870

Bravo

AF:

0.509

Asia WGS

AF:

0.472

AC:

1640

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Benign

0.72

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