rs3825973

Variant names:

• chr15-63042436-C-G
• rs3825973
• ENST00000804116.1:n.122+6129G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-63042436-C-G
• chr15-63042436-C-A
• chr15-63042436-C-T

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+6129G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 151,922 control chromosomes in the GnomAD database, including 1,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (1492 hom., cov: 33)
• Consequence: TPM1-AS ENST00000804116.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.675
• Publications: 2 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)
• 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=-0.81).
• BP6: Variant 15-63042436-C-G is Benign according to our data. Variant chr15-63042436-C-G is described in ClinVar as Benign. ClinVar VariationId is 668729.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 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+6129G>C		intron	N/A
	TPM1-AS	ENST00000804117.1		n.171+952G>C		intron	N/A
	TPM1	ENST00000288398.10	TSL:1	c.-394C>G		upstream_gene	N/A	ENSP00000288398.6	P09493-10

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18260 AN: 151808 Hom.: 1483 Cov.: 33

Gnomad AFR AF: 0.0784

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0796

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0621

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.120 AC: 18287 AN: 151922 Hom.: 1492 Cov.: 33 AF XY: 0.127 AC XY: 9467 AN XY: 74286

African (AFR) AF: 0.0784 AC: 3251 AN: 41464

American (AMR) AF: 0.112 AC: 1720 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0796 AC: 276 AN: 3466

East Asian (EAS) AF: 0.439 AC: 2241 AN: 5110

South Asian (SAS) AF: 0.306 AC: 1474 AN: 4822

European-Finnish (FIN) AF: 0.127 AC: 1339 AN: 10576

Middle Eastern (MID) AF: 0.0634 AC: 18 AN: 284

European-Non Finnish (NFE) AF: 0.112 AC: 7636 AN: 67888

Other (OTH) AF: 0.120 AC: 253 AN: 2106

Alfa AF: 0.0608 Hom.: 58

Bravo AF: 0.116

Asia WGS AF: 0.370 AC: 1280 AN: 3470

ClinVar

ClinVar submissions

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	-0.81
CADD	Benign	3.2
DANN	Benign	0.61
PhyloP100		-0.68
PromoterAI		0.030	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3825973; hg19: chr15-63334635;