Variant chr2-39666185-C-T 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.211C>T(p.Pro71Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000754 in 1,459,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

TMEM178A
NM_152390.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.729

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:

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=0.06939638).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM178A	NM_152390.3 linkuse as main transcript	c.211C>T	p.Pro71Ser	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.211C>T	p.Pro71Ser	missense_variant	1/4	1	NM_152390.3	ENSP00000281961	P1	Q8NBL3-1
TMEM178A	ENST00000437068.5 linkuse as main transcript	n.367+837C>T		intron_variant, non_coding_transcript_variant		4
TMEM178A	ENST00000482239.5 linkuse as main transcript	n.143+545C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151378

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000765

AC:

AN:

1307934

Hom.:

Cov.:

AF XY:

0.00000776

AC XY:

AN XY:

644204

show subpopulations

Gnomad4 AFR exome

AF:

0.0000755

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000143

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000576

Gnomad4 OTH exome

AF:

0.0000185

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151378

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73914

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Apr 30, 2024

The c.211C>T (p.P71S) alteration is located in exon 1 (coding exon 1) of the TMEM178A gene. This alteration results from a C to T substitution at nucleotide position 211, causing the proline (P) at amino acid position 71 to be replaced by a serine (S). 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

0.061

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0042

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.35

M_CAP

Pathogenic

0.67

MetaRNN

Benign

0.069

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

MutationTaster

Benign

0.60

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

0.54

REVEL

Benign

0.054

Sift

Benign

0.55

Sift4G

Benign

0.53

Polyphen

0.0

Vest4

0.11

MutPred

0.26

Loss of catalytic residue at P71 (P = 0.0043);

MVP

0.043

MPC

0.80

ClinPred

0.11

GERP RS

2.3

Varity_R

0.057

gMVP

0.47

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