Variant chr7-141074398-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001195278.2(TMEM178B):c.88C>T(p.His30Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000578 in 1,383,778 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: not found (cov: 33)

Exomes 𝑓: 0.0000058 ( 0 hom. )

Consequence

TMEM178B
NM_001195278.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.43

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36582565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TMEM178B	NM_001195278.2 linkuse as main transcript	c.88C>T	p.His30Tyr	missense_variant	1/4	ENST00000565468.6
TMEM178B	XM_011515705.3 linkuse as main transcript	c.88C>T	p.His30Tyr	missense_variant	1/4
TMEM178B	XM_017011636.2 linkuse as main transcript	c.88C>T	p.His30Tyr	missense_variant	1/4
TMEM178B	XR_001744505.2 linkuse as main transcript	n.335C>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.88C>T	p.His30Tyr	missense_variant	1/4	5	NM_001195278.2	P1
TMEM178B	ENST00000563442.1 linkuse as main transcript	n.6C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000730

AC:

AN:

136916

Hom.:

AF XY:

0.00

AC XY:

AN XY:

74438

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:

0.0000186

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000578

AC:

AN:

1383778

Hom.:

Cov.:

AF XY:

0.00000586

AC XY:

AN XY:

682838

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:

0.00000742

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 25, 2022

The c.88C>T (p.H30Y) 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 88, causing the histidine (H) at amino acid position 30 to be replaced by a tyrosine (Y). 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

0.25

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.034

T;T

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.93

D;D

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.37

T;T

MutationAssessor

Benign

1.3

L;.

MutationTaster

Benign

0.97

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-2.0

N;.

Sift

Benign

0.18

T;.

Sift4G

Benign

0.25

T;T

Vest4

0.31

MVP

0.51

GERP RS

4.5

Varity_R

0.22

gMVP

0.85

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