Variant chr17-44014937-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.16G>A(p.Gly6Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,460,022 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: not found (cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

TMEM101
NM_032376.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.56

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:

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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=0.18313989).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TMEM101	NM_032376.4 linkuse as main transcript	c.16G>A	p.Gly6Ser	missense_variant	1/4	ENST00000206380.8	NP_115752.1
TMEM101	NM_001304813.2 linkuse as main transcript	c.-38+47G>A		intron_variant			NP_001291742.1
TMEM101	NM_001304814.2 linkuse as main transcript	c.-38+47G>A		intron_variant			NP_001291743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM101	ENST00000206380.8 linkuse as main transcript	c.16G>A	p.Gly6Ser	missense_variant	1/4	1	NM_032376.4	ENSP00000206380	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000802

AC:

AN:

249478

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134968

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1460022

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726242

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:

0.0000171

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000225

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Jan 10, 2023

The c.16G>A (p.G6S) alteration is located in exon 1 (coding exon 1) of the TMEM101 gene. This alteration results from a G to A substitution at nucleotide position 16, causing the glycine (G) at amino acid position 6 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

0.093

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.033

T;T;T

Eigen

Benign

-0.041

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.79

.;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;.

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.6

.;N;.

REVEL

Benign

0.25

Sift

Benign

0.11

.;T;.

Sift4G

Benign

0.56

T;T;T

Polyphen

0.69

P;P;.

Vest4

0.28

MutPred

0.23

Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);

MVP

0.18

MPC

1.3

ClinPred

0.69

GERP RS

4.8

Varity_R

0.090

gMVP

0.21

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