Variant 19-42316895-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173633.3(TMEM145):c.832G>A(p.Val278Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,613,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

TMEM145
NM_173633.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.12

Variant links:

Genes affected

TMEM145 (HGNC:26912): (transmembrane protein 145) Predicted to be involved in G protein-coupled receptor signaling pathway and response to pheromone. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM145 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20770049).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM145	NM_173633.3 linkuse as main transcript	c.832G>A	p.Val278Met	missense_variant	11/15	ENST00000301204.8	NP_775904.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TMEM145	ENST00000301204.8 linkuse as main transcript	c.832G>A	p.Val278Met	missense_variant	11/15	2	NM_173633.3	ENSP00000301204
TMEM145	ENST00000673205.1 linkuse as main transcript	c.832G>A	p.Val278Met	missense_variant	11/14			ENSP00000499841
TMEM145	ENST00000673187.1 linkuse as main transcript	c.874G>A	p.Val292Met	missense_variant	11/15			ENSP00000500040	P1
TMEM145	ENST00000598766.1 linkuse as main transcript	c.904G>A	p.Val302Met	missense_variant	11/14	5		ENSP00000470827

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.0000399

AC:

AN:

250616

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.000493

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000267

AC:

AN:

1461382

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

727038

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000164

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.000386

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.0000762

Hom.:

Bravo

AF:

0.000193

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Dec 12, 2023

The c.832G>A (p.V278M) alteration is located in exon 11 (coding exon 11) of the TMEM145 gene. This alteration results from a G to A substitution at nucleotide position 832, causing the valine (V) at amino acid position 278 to be replaced by a methionine (M). 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

Uncertain

0.46

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.045

T;.

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.037

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.9

L;.

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.8

N;.

REVEL

Benign

0.16

Sift

Uncertain

0.013

D;.

Sift4G

Uncertain

0.036

D;D

Polyphen

0.79

P;.

Vest4

0.70

MVP

0.25

MPC

1.2

ClinPred

0.13

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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