Variant chr17-44014401-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_032376.4(TMEM101):c.274G>A(p.Ala92Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000926 in 1,555,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

TMEM101
NM_032376.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.01

Variant links:

Genes affected

TMEM101 (HGNC:28653): (transmembrane protein 101) Involved in positive regulation of I-kappaB kinase/NF-kappaB signaling. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM101 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=0.09818843).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM101	NM_032376.4 linkuse as main transcript	c.274G>A	p.Ala92Thr	missense_variant	2/4	ENST00000206380.8	NP_115752.1	Q96IK0
TMEM101	NM_001304813.2 linkuse as main transcript	c.100G>A	p.Ala34Thr	missense_variant	3/5		NP_001291742.1	Q96IK0B4DFS4
TMEM101	NM_001304814.2 linkuse as main transcript	c.100G>A	p.Ala34Thr	missense_variant	3/5		NP_001291743.1	Q96IK0B4DFS4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM101	ENST00000206380.8 linkuse as main transcript	c.274G>A	p.Ala92Thr	missense_variant	2/4	1	NM_032376.4	ENSP00000206380.3		Q96IK0

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000118

AC:

AN:

160686

Hom.:

AF XY:

0.000141

AC XY:

AN XY:

85004

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000199

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000432

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000190

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.0000884

AC:

124

AN:

1402824

Hom.:

Cov.:

AF XY:

0.0000852

AC XY:

AN XY:

692310

show subpopulations

Gnomad4 AFR exome

AF:

0.0000314

Gnomad4 AMR exome

AF:

0.000222

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000628

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000870

Gnomad4 OTH exome

AF:

0.000206

GnomAD4 genome

AF:

0.000131

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000957

Hom.:

Bravo

AF:

0.000140

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000236

AC:

ExAC

AF:

0.0000267

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

Jul 09, 2021

The c.274G>A (p.A92T) alteration is located in exon 2 (coding exon 2) of the TMEM101 gene. This alteration results from a G to A substitution at nucleotide position 274, causing the alanine (A) at amino acid position 92 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

Benign

0.13

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.035

T;T;T;.;.;.

Eigen

Benign

-0.089

Eigen_PC

Benign

-0.0064

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.81

.;T;T;T;T;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.098

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

L;L;.;.;.;.

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.72

.;N;.;.;.;.

REVEL

Benign

0.022

Sift

Benign

0.24

.;T;.;.;.;.

Sift4G

Benign

0.30

T;T;T;T;.;.

Polyphen

0.73

P;P;.;.;.;.

Vest4

0.38

MVP

0.12

MPC

0.44

ClinPred

0.065

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.051

gMVP

0.71

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