ENST00000804116.1:n.122+6155G>C

Variant names:

• chr15-63042410-C-G
• rs3809568
• ENST00000804116.1:n.122+6155G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000804116.1(TPM1-AS):​n.122+6155G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,224 control chromosomes in the GnomAD database, including 1,569 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (1569 hom., cov: 33)
• Consequence: TPM1-AS ENST00000804116.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.09
• Publications: 1 publications found

Genes affected

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

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 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• hypertrophic cardiomyopathy 3

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
• dilated cardiomyopathy 1Y

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• dilated cardiomyopathy

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• left ventricular noncompaction

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• arrhythmogenic right ventricular cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 15-63042410-C-G is Benign according to our data. Variant chr15-63042410-C-G is described in ClinVar as Benign. ClinVar VariationId is 668728.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000804116.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPM1-AS	ENST00000804116.1		n.122+6155G>C		intron	N/A
	TPM1-AS	ENST00000804117.1		n.171+978G>C		intron	N/A
	TPM1	ENST00000288398.10	TSL:1	c.-420C>G		upstream_gene	N/A	ENSP00000288398.6	P09493-10

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18696 AN: 152106 Hom.: 1560 Cov.: 33

Gnomad AFR AF: 0.0847

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0807

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.123 AC: 18725 AN: 152224 Hom.: 1569 Cov.: 33 AF XY: 0.130 AC XY: 9671 AN XY: 74418

African (AFR) AF: 0.0847 AC: 3519 AN: 41560

American (AMR) AF: 0.115 AC: 1767 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0807 AC: 280 AN: 3468

East Asian (EAS) AF: 0.450 AC: 2308 AN: 5126

South Asian (SAS) AF: 0.314 AC: 1516 AN: 4828

European-Finnish (FIN) AF: 0.126 AC: 1334 AN: 10612

Middle Eastern (MID) AF: 0.0616 AC: 18 AN: 292

European-Non Finnish (NFE) AF: 0.112 AC: 7640 AN: 68000

Other (OTH) AF: 0.125 AC: 264 AN: 2116

Alfa AF: 0.0654 Hom.: 67

Bravo AF: 0.120

Asia WGS AF: 0.379 AC: 1310 AN: 3466

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.6
DANN	Benign	0.62
PhyloP100		-1.1
PromoterAI		-0.011	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3809568; hg19: chr15-63334609;