rs930569425

Variant names:

• chr15-63042757-C-T
• rs930569425
• NM_001018005.2:c.-73C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-63042757-C-T
• chr15-63042757-C-G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001018005.2(TPM1):​c.-73C>T variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.0000268 in 1,306,376 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000029 (1 hom.)
• Consequence: TPM1 NM_001018005.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.58
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 15-63042757-C-T is Benign according to our data. Variant chr15-63042757-C-T is described in ClinVar as Benign. ClinVar VariationId is 1241219.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 34 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001018005.2. 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.-73C>T		5_prime_UTR	Exon 1 of 10	NP_001018005.1	D9YZV4
	TPM1	NM_001365778.1		c.-73C>T		5_prime_UTR	Exon 1 of 10	NP_001352707.1	Q6ZN40
	TPM1	NM_001407322.1		c.-73C>T		5_prime_UTR	Exon 1 of 11	NP_001394251.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPM1	ENST00000403994.9	TSL:1 MANE Select	c.-73C>T		5_prime_UTR	Exon 1 of 10	ENSP00000385107.4	P09493-1
	TPM1	ENST00000288398.10	TSL:1	c.-73C>T		5_prime_UTR	Exon 1 of 10	ENSP00000288398.6	P09493-10
	TPM1	ENST00000358278.7	TSL:1	c.-73C>T		5_prime_UTR	Exon 1 of 9	ENSP00000351022.3	P09493-3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000295 AC: 34 AN: 1154174 Hom.: 1 Cov.: 16 AF XY: 0.0000308 AC XY: 18 AN XY: 583474

African (AFR) AF: 0.00 AC: 0 AN: 27266

American (AMR) AF: 0.0000266 AC: 1 AN: 37636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23502

East Asian (EAS) AF: 0.00 AC: 0 AN: 36752

South Asian (SAS) AF: 0.00 AC: 0 AN: 77120

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4304

European-Non Finnish (NFE) AF: 0.0000389 AC: 33 AN: 848042

Other (OTH) AF: 0.00 AC: 0 AN: 50000

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74346

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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	-0.43
CADD	Benign	16
DANN	Benign	0.95
PhyloP100		4.6
PromoterAI		0.098	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=254/46	polymorphism

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: rs930569425; hg19: chr15-63334956;