Variant 2-39666095-G-C 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_152390.3(TMEM178A):c.121G>C(p.Glu41Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000099 in 1,414,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000099 ( 0 hom. )

Consequence

TMEM178A
NM_152390.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.67

Variant links:

Genes affected

TMEM178A (HGNC:28517): (transmembrane protein 178A) Predicted to be involved in negative regulation of osteoclast differentiation and regulation of cytosolic calcium ion concentration. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM178A links:

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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=0.21609196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM178A	NM_152390.3 linkuse as main transcript	c.121G>C	p.Glu41Gln	missense_variant	1/4	ENST00000281961.3	NP_689603.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM178A	ENST00000281961.3 linkuse as main transcript	c.121G>C	p.Glu41Gln	missense_variant	1/4	1	NM_152390.3	ENSP00000281961	P1	Q8NBL3-1
TMEM178A	ENST00000437068.5 linkuse as main transcript	n.367+747G>C		intron_variant, non_coding_transcript_variant		4
TMEM178A	ENST00000482239.5 linkuse as main transcript	n.143+455G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000271

AC:

AN:

184748

Hom.:

AF XY:

0.0000384

AC XY:

AN XY:

104058

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:

0.000199

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000990

AC:

AN:

1414626

Hom.:

Cov.:

AF XY:

0.0000171

AC XY:

AN XY:

702858

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:

0.000160

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000341

AC:

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

Jun 10, 2024

The c.121G>C (p.E41Q) alteration is located in exon 1 (coding exon 1) of the TMEM178A gene. This alteration results from a G to C substitution at nucleotide position 121, causing the glutamic acid (E) at amino acid position 41 to be replaced by a glutamine (Q). 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

0.14

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

T;.

Eigen

Benign

0.084

Eigen_PC

Benign

0.067

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.68

T;T

M_CAP

Pathogenic

0.87

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.52

MutationAssessor

Benign

2.0

M;M

MutationTaster

Benign

0.99

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.89

N;.

REVEL

Benign

0.11

Sift

Uncertain

0.010

D;.

Sift4G

Uncertain

0.022

D;D

Polyphen

0.76

P;P

Vest4

0.18

MutPred

0.26

Loss of ubiquitination at K40 (P = 0.0328);Loss of ubiquitination at K40 (P = 0.0328);

MVP

0.13

MPC

0.89

ClinPred

0.17

GERP RS

3.2

Varity_R

0.21

gMVP

0.42

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