chr15-63042678-T-G

Variant names:

• chr15-63042678-T-G
• rs2140590601
• ENST00000288398.10:c.-152T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The ENST00000288398.10(TPM1):​c.-152T>G variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00000204 in 490,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: TPM1 ENST00000288398.10 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.62
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP6: Variant 15-63042678-T-G is Benign according to our data. Variant chr15-63042678-T-G is described in ClinVar as Benign. ClinVar VariationId is 1246057.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000288398.10. 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
	TPM1	NM_001018005.2	MANE Select	c.-152T>G		upstream_gene	N/A	NP_001018005.1	D9YZV4
	TPM1	NM_001365778.1		c.-152T>G		upstream_gene	N/A	NP_001352707.1	Q6ZN40
	TPM1	NM_001407322.1		c.-152T>G		upstream_gene	N/A	NP_001394251.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPM1	ENST00000288398.10	TSL:1	c.-152T>G		5_prime_UTR	Exon 1 of 10	ENSP00000288398.6	P09493-10
	TPM1	ENST00000893958.1		c.-152T>G		5_prime_UTR	Exon 1 of 10	ENSP00000564017.1
	TPM1	ENST00000559831.6	TSL:5	n.-152T>G		non_coding_transcript_exon	Exon 1 of 10	ENSP00000452977.2	H0YKX5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000204 AC: 1 AN: 490746 Hom.: 0 Cov.: 5 AF XY: 0.00000380 AC XY: 1 AN XY: 263026

African (AFR) AF: 0.00 AC: 0 AN: 11926

American (AMR) AF: 0.00 AC: 0 AN: 22804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14572

East Asian (EAS) AF: 0.00 AC: 0 AN: 30014

South Asian (SAS) AF: 0.0000198 AC: 1 AN: 50384

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39936

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2100

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 292114

Other (OTH) AF: 0.00 AC: 0 AN: 26896

GnomAD4 genome Cov.: 33

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	-0.24
CADD	Benign	21
DANN	Benign	0.92
PhyloP100		3.6
PromoterAI		-0.31	Neutral

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

Other links and lift over

dbSNP: rs2140590601; hg19: chr15-63334877;