rs879682441

Variant names:

• chr15-63042555-G-GGAGGGCC
• rs879682441
• NM_001018005.2:c.-275_-274insGAGGGCC

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001018005.2(TPM1):​c.-275_-274insGAGGGCC variant causes a upstream gene 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 NM_001018005.2 upstream_gene
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.87

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1691 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPM1	NM_001018005.2	c.-275_-274insGAGGGCC		upstream_gene_variant		ENST00000403994.9	NP_001018005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPM1	ENST00000403994.9	c.-275_-274insGAGGGCC		upstream_gene_variant		1	NM_001018005.2	ENSP00000385107.4

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

Gnomad4 AFR exome AF: 0.00135

Gnomad4 AMR exome AF: 0.00307

Gnomad4 ASJ exome AF: 0.00842

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000572

Gnomad4 FIN exome AF: 0.0296

Gnomad4 NFE exome AF: 0.0121

Gnomad4 OTH exome AF: 0.00960

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

Gnomad4 AFR AF: 0.00262

Gnomad4 AMR AF: 0.00301

Gnomad4 ASJ AF: 0.0156

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0466

Gnomad4 NFE AF: 0.0140

Gnomad4 OTH AF: 0.00898

Alfa AF: 0.00428 Hom.: 1

Asia WGS AF: 0.00116 AC: 5 AN: 3472

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs879682441; hg19: chr15-63334754;