NM_001018005.2:c.5_8delCTTT

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001018005.2(TPM1):c.*5_*8delCTTT variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0000125 in 1,601,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). The gene TPM1 is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.000028 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

TPM1
NM_001018005.2 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4

Conservation

PhyloP100: 4.60

Publications

1 publications found

Variant links:

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 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

TPM1 links:

Genome browser will be placed here

ACMG classification

Specifications for TPM1 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 16 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TPM1	NM_001018005.2	MANE Select	c.5_8delCTTT		3_prime_UTR	Exon 10 of 10	NP_001018005.1	D9YZV4
TPM1	NM_001365777.1		c.781_784delCTTT	p.Leu261AlafsTer33	frameshift	Exon 9 of 9	NP_001352706.1
TPM1	NM_001407327.1		c.781_784delCTTT	p.Leu261AlafsTer33	frameshift	Exon 9 of 9	NP_001394256.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TPM1	ENST00000403994.9	TSL:1 MANE Select	c.5_8delCTTT	3_prime_UTR	Exon 10 of 10	ENSP00000385107.4	P09493-1
TPM1	ENST00000288398.10	TSL:1	c.53_56delCTTT	3_prime_UTR	Exon 10 of 10	ENSP00000288398.6	P09493-10
TPM1	ENST00000560970.6	TSL:1	c.53_56delCTTT	3_prime_UTR	Exon 10 of 10	ENSP00000453062.2	A0A0S2Z4G6

Frequencies

GnomAD3 genomes

AF:

0.0000275

AC:

AN:

145394

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000706

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:

0.0000448

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000123

AC:

AN:

244404

AF XY:

0.0000151

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000271

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1456498

Hom.:

AF XY:

0.00000828

AC XY:

AN XY:

724424

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33378

American (AMR)

AF:

0.0000225

AC:

AN:

44494

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26004

East Asian (EAS)

AF:

0.00

AC:

AN:

39558

South Asian (SAS)

AF:

0.00

AC:

AN:

85772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51460

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00000991

AC:

AN:

1109902

Other (OTH)

AF:

0.0000665

AC:

AN:

60174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.413

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000275

AC:

AN:

145394

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

70248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38924

American (AMR)

AF:

0.0000706

AC:

AN:

14174

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3426

East Asian (EAS)

AF:

0.00

AC:

AN:

4954

South Asian (SAS)

AF:

0.00

AC:

AN:

4648

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.0000448

AC:

AN:

66918

Other (OTH)

AF:

0.00

AC:

AN:

1982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cardiomyopathy (2)

Cardiovascular phenotype (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.6

Mutation Taster

=97/3

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over