Variant 19-16076055-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001145160.2(TPM4):c.123G>A(p.Glu41Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00271 in 1,608,824 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 37 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 45 hom. )

Consequence

TPM4
NM_001145160.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.184

Variant links:

Genes affected

TPM4 (HGNC:12013): (tropomyosin 4) This gene encodes a member of the tropomyosin family of actin-binding proteins involved in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle cells. Tropomyosins are dimers of coiled-coil proteins that polymerize end-to-end along the major groove in most actin filaments. They provide stability to the filaments and regulate access of other actin-binding proteins. In muscle cells, they regulate muscle contraction by controlling the binding of myosin heads to the actin filament. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2009]

TPM4 links:

ENSG00000279198 (HGNC:):

ENSG00000279198 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 19-16076055-G-A is Benign according to our data. Variant chr19-16076055-G-A is described in ClinVar as [Benign]. Clinvar id is 768977.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.184 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0134 (2039/152314) while in subpopulation AFR AF= 0.0458 (1903/41552). AF 95% confidence interval is 0.0441. There are 37 homozygotes in gnomad4. There are 979 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2039 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPM4	NM_001145160.2 link	c.123G>A	p.Glu41Glu	synonymous_variant	Exon 2 of 9		NP_001138632.1	P67936-2
TPM4	NM_001367836.1 link	c.75G>A	p.Glu25Glu	synonymous_variant	Exon 2 of 9		NP_001354765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
TPM4	ENST00000646974.2 link	c.123G>A	p.Glu41Glu	synonymous_variant	Exon 2 of 9		ENSP00000494125.1	P67936-2
TPM4	ENST00000647464.2 link	c.15G>A	p.Glu5Glu	synonymous_variant	Exon 2 of 10		ENSP00000496648.3	A0A2R8YHD2
TPM4	ENST00000589897.1 link	c.123G>A	p.Glu41Glu	synonymous_variant	Exon 3 of 3	4	ENSP00000466158.1	K7ELP0

Frequencies

GnomAD3 genomes

AF:

0.0134

AC:

2036

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00634

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00333

AC:

795

AN:

238662

Hom.:

AF XY:

0.00257

AC XY:

334

AN XY:

129956

show subpopulations

Gnomad AFR exome

AF:

0.0484

Gnomad AMR exome

AF:

0.00268

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000343

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000241

Gnomad OTH exome

AF:

0.00189

GnomAD4 exome

AF:

0.00160

AC:

2327

AN:

1456510

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

995

AN XY:

723970

show subpopulations

Gnomad4 AFR exome

AF:

0.0497

Gnomad4 AMR exome

AF:

0.00333

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000706

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000286

Gnomad4 OTH exome

AF:

0.00299

GnomAD4 genome

AF:

0.0134

AC:

2039

AN:

152314

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

979

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0458

Gnomad4 AMR

AF:

0.00633

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00992

Alfa

AF:

0.00720

Hom.:

Bravo

AF:

0.0162

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.95

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over