Variant 7-141074678-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_001195278.2(TMEM178B):c.368C>T(p.Ala123Val) variant causes a missense change. The variant allele was found at a frequency of 0.000289 in 1,505,436 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00030 ( 1 hom. )

Consequence

TMEM178B
NM_001195278.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.31

Variant links:

Genes affected

TMEM178B (HGNC:44112): (transmembrane protein 178B) Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM178B 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=0.12031144).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TMEM178B	NM_001195278.2 linkuse as main transcript	c.368C>T	p.Ala123Val	missense_variant	1/4	ENST00000565468.6
TMEM178B	XM_011515705.3 linkuse as main transcript	c.368C>T	p.Ala123Val	missense_variant	1/4
TMEM178B	XM_017011636.2 linkuse as main transcript	c.368C>T	p.Ala123Val	missense_variant	1/4
TMEM178B	XR_001744505.2 linkuse as main transcript	n.615C>T		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM178B	ENST00000565468.6 linkuse as main transcript	c.368C>T	p.Ala123Val	missense_variant	1/4	5	NM_001195278.2	P1
TMEM178B	ENST00000563442.1 linkuse as main transcript	n.286C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.000353

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000944

AC:

AN:

116494

Hom.:

AF XY:

0.000127

AC XY:

AN XY:

63202

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000460

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:

0.000197

Gnomad OTH exome

AF:

0.000280

GnomAD4 exome

AF:

0.000302

AC:

409

AN:

1353208

Hom.:

Cov.:

AF XY:

0.000291

AC XY:

193

AN XY:

663300

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000607

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:

0.000363

Gnomad4 OTH exome

AF:

0.000391

GnomAD4 genome

AF:

0.000171

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0000482

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:

0.000353

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000299

Hom.:

Bravo

AF:

0.000189

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

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

Mar 27, 2023

The c.368C>T (p.A123V) alteration is located in exon 1 (coding exon 1) of the TMEM178B gene. This alteration results from a C to T substitution at nucleotide position 368, causing the alanine (A) at amino acid position 123 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

0.10

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.39

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0086

T;T

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.079

MetaRNN

Benign

0.12

T;T

MutationAssessor

Benign

0.69

N;.

MutationTaster

Benign

0.75

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.80

N;.

Sift

Benign

0.18

T;.

Sift4G

Benign

0.29

T;T

Vest4

0.091

MVP

0.48

GERP RS

3.7

Varity_R

0.10

gMVP

0.70

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