chr15-63071538-T-C

Position:

• chr15-63071538-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000267996.11(TPM1):​c.*366T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 338,988 control chromosomes in the GnomAD database, including 2,966 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 0.12 (1313 hom., cov: 33)
  • Exomes 𝑓: 0.12 (1653 hom.)
• Consequence: TPM1 ENST00000267996.11 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPM1	NM_001018004.2	c.*366T>C		3_prime_UTR_variant	9/9
TPM1	NM_001018006.2	c.*366T>C		3_prime_UTR_variant	9/9
TPM1	NM_001018007.2	c.*366T>C		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000558905.1	n.254+120A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17747 AN: 152158 Hom.: 1305 Cov.: 33

Gnomad AFR AF: 0.0841

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.0957

Gnomad EAS AF: 0.00288

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0574

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.117

GnomAD4 exome AF: 0.120 AC: 22475 AN: 186712 Hom.: 1653 Cov.: 0 AF XY: 0.119 AC XY: 12179 AN XY: 101940

Gnomad4 AFR exome AF: 0.0807

Gnomad4 AMR exome AF: 0.295

Gnomad4 ASJ exome AF: 0.0882

Gnomad4 EAS exome AF: 0.00140

Gnomad4 SAS exome AF: 0.108

Gnomad4 FIN exome AF: 0.0627

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.117 AC: 17767 AN: 152276 Hom.: 1313 Cov.: 33 AF XY: 0.114 AC XY: 8494 AN XY: 74462

Gnomad4 AFR AF: 0.0839

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.0957

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.0574

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.115

Alfa AF: 0.129 Hom.: 2105

Bravo AF: 0.126

Asia WGS AF: 0.0490 AC: 171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	13
DANN	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs707602; hg19: chr15-63363737;