rs879682441

Variant names:

• chr15-63042555-G-GGAGGGCC
• rs879682441
• ENST00000893958.1:c.-274_-273insAGGGCCG

Your query was ambiguous. Multiple possible variants found:

• chr15-63042555-G-GGAGGGCC
• chr15-63042555-G-GGAGGGCCGGCGGCC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000893958.1(TPM1):​c.-274_-273insAGGGCCG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 408,560 control chromosomes in the GnomAD database, including 43 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (26 hom., cov: 32)
  • Exomes 𝑓: 0.0096 (17 hom.)
• Consequence: TPM1 ENST00000893958.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.87
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 15-63042555-G-GGAGGGCC is Benign according to our data. Variant chr15-63042555-G-GGAGGGCC is described in ClinVar as Likely_benign. ClinVar VariationId is 1220336.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0111 (1691/152188) while in subpopulation NFE AF = 0.014 (954/67960). AF 95% confidence interval is 0.0133. There are 26 homozygotes in GnomAd4. There are 906 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1691 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000893958.1. 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
	TPM1	NM_001018005.2	MANE Select	c.-275_-274insGAGGGCC		upstream_gene	N/A	NP_001018005.1	D9YZV4
	TPM1	NM_001365778.1		c.-275_-274insGAGGGCC		upstream_gene	N/A	NP_001352707.1	Q6ZN40
	TPM1	NM_001407322.1		c.-275_-274insGAGGGCC		upstream_gene	N/A	NP_001394251.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPM1	ENST00000893958.1		c.-274_-273insAGGGCCG		5_prime_UTR	Exon 1 of 10	ENSP00000564017.1
	TPM1-AS	ENST00000804116.1		n.122+6009_122+6010insGGCCCTC		intron	N/A
	TPM1-AS	ENST00000804117.1		n.171+832_171+833insGGCCCTC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0111 AC: 1691 AN: 152080 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.00263

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0466

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0140

Gnomad OTH AF: 0.00907

GnomAD4 exome AF: 0.00958 AC: 2456 AN: 256372 Hom.: 17 AF XY: 0.00836 AC XY: 1174 AN XY: 140394

African (AFR) AF: 0.00135 AC: 7 AN: 5180

American (AMR) AF: 0.00307 AC: 35 AN: 11386

Ashkenazi Jewish (ASJ) AF: 0.00842 AC: 55 AN: 6532

East Asian (EAS) AF: 0.00 AC: 0 AN: 12926

South Asian (SAS) AF: 0.000572 AC: 24 AN: 41954

European-Finnish (FIN) AF: 0.0296 AC: 368 AN: 12420

Middle Eastern (MID) AF: 0.000996 AC: 1 AN: 1004

European-Non Finnish (NFE) AF: 0.0121 AC: 1836 AN: 151428

Other (OTH) AF: 0.00960 AC: 130 AN: 13542

GnomAD4 genome AF: 0.0111 AC: 1691 AN: 152188 Hom.: 26 Cov.: 32 AF XY: 0.0122 AC XY: 906 AN XY: 74418

African (AFR) AF: 0.00262 AC: 109 AN: 41554

American (AMR) AF: 0.00301 AC: 46 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 54 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.0466 AC: 494 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0140 AC: 954 AN: 67960

Other (OTH) AF: 0.00898 AC: 19 AN: 2116

Alfa AF: 0.00428 Hom.: 1

Asia WGS AF: 0.00116 AC: 5 AN: 3472

ClinVar

ClinVar submissions

Significance: Likely 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
PhyloP100		2.9

Splicing

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

Other links and lift over

dbSNP: rs879682441; hg19: chr15-63334754; COSMIC: COSV51260955;