Variant 1-151171697-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000295314.9(TMOD4):c.554A>T(p.Glu185Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

TMOD4
ENST00000295314.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.99

Variant links:

Genes affected

TMOD4 (HGNC:11874): (tropomodulin 4) Predicted to enable tropomyosin binding activity. Predicted to be involved in actin filament organization; muscle contraction; and myofibril assembly. Located in striated muscle thin filament. [provided by Alliance of Genome Resources, Apr 2022]

TMOD4 links:

TMOD4 (HGNC:):

TMOD4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMOD4	NM_013353.3 linkuse as main transcript	c.554A>T	p.Glu185Val	missense_variant	6/10	ENST00000295314.9	NP_037485.2	Q9NZQ9-1
TMOD4	XM_011509449.2 linkuse as main transcript	c.554A>T	p.Glu185Val	missense_variant	6/10		XP_011507751.1	Q9NZQ9-1
TMOD4	XM_047418672.1 linkuse as main transcript	c.554A>T	p.Glu185Val	missense_variant	5/9		XP_047274628.1
TMOD4	XM_017001090.3 linkuse as main transcript	c.554A>T	p.Glu185Val	missense_variant	6/8		XP_016856579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMOD4	ENST00000295314.9 linkuse as main transcript	c.554A>T	p.Glu185Val	missense_variant	6/10	1	NM_013353.3	ENSP00000295314.4		Q9NZQ9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251464

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135906

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 18, 2023

The c.554A>T (p.E185V) alteration is located in exon 6 (coding exon 5) of the TMOD4 gene. This alteration results from a A to T substitution at nucleotide position 554, causing the glutamic acid (E) at amino acid position 185 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.072

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.74

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.74

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-4.4

REVEL

Benign

0.19

Sift

Benign

0.065

Sift4G

Uncertain

0.025

Polyphen

0.98

Vest4

0.66

MutPred

0.52

Loss of ubiquitination at K188 (P = 0.0374);

MVP

0.61

MPC

0.40

ClinPred

0.95

GERP RS

5.7

Varity_R

0.66

gMVP

0.64

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