Variant chr7-141212597-T-C 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.389T>C(p.Ile130Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000371 in 1,535,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

TMEM178B
NM_001195278.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.49

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:

TMEM178B (HGNC:):

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=0.36192828).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TMEM178B	NM_001195278.2 linkuse as main transcript	c.389T>C	p.Ile130Thr	missense_variant	2/4	ENST00000565468.6	NP_001182207.1
TMEM178B	XM_011515705.3 linkuse as main transcript	c.389T>C	p.Ile130Thr	missense_variant	2/4		XP_011514007.1
TMEM178B	XM_017011636.2 linkuse as main transcript	c.389T>C	p.Ile130Thr	missense_variant	2/4		XP_016867125.1
TMEM178B	XR_001744505.2 linkuse as main transcript	n.636T>C		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM178B	ENST00000565468.6 linkuse as main transcript	c.389T>C	p.Ile130Thr	missense_variant	2/4	5	NM_001195278.2	ENSP00000456594.1		H3BS89
TMEM178B	ENST00000563442.1 linkuse as main transcript	n.307T>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000372

AC:

AN:

134484

Hom.:

AF XY:

0.0000137

AC XY:

AN XY:

73230

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:

0.0000947

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000369

AC:

AN:

1383680

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

682814

show subpopulations

Gnomad4 AFR exome

AF:

0.0000633

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:

0.000148

Gnomad4 NFE exome

AF:

0.0000389

Gnomad4 OTH exome

AF:

0.0000345

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000882

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

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

Nov 26, 2024

The c.389T>C (p.I130T) alteration is located in exon 2 (coding exon 2) of the TMEM178B gene. This alteration results from a T to C substitution at nucleotide position 389, causing the isoleucine (I) at amino acid position 130 to be replaced by a threonine (T). 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

0.38

BayesDel_addAF

Benign

0.0075

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.010

T;T

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

T;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.36

T;T

MutationAssessor

Benign

1.8

L;.

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.88

N;.

Sift

Benign

0.059

T;.

Sift4G

Benign

0.17

T;T

Vest4

0.62

MVP

0.41

GERP RS

5.2

Varity_R

0.13

gMVP

0.74

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