Variant 12-44376713-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032256.3(TMEM117):c.887T>C(p.Ile296Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000494 in 1,608,724 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00083 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00046 ( 6 hom. )

Consequence

TMEM117
NM_032256.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.48

Variant links:

Genes affected

TMEM117 (HGNC:25308): (transmembrane protein 117) Involved in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress. Located in endoplasmic reticulum and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM117 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00911504).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM117	NM_032256.3 linkuse as main transcript	c.887T>C	p.Ile296Thr	missense_variant	7/8	ENST00000266534.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM117	ENST00000266534.8 linkuse as main transcript	c.887T>C	p.Ile296Thr	missense_variant	7/8	1	NM_032256.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000828

AC:

126

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00952

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000722

AC:

177

AN:

245022

Hom.:

AF XY:

0.000704

AC XY:

AN XY:

132192

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000482

Gnomad ASJ exome

AF:

0.00849

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000486

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000502

Gnomad OTH exome

AF:

0.00134

GnomAD4 exome

AF:

0.000459

AC:

669

AN:

1456372

Hom.:

Cov.:

AF XY:

0.000485

AC XY:

351

AN XY:

724210

show subpopulations

Gnomad4 AFR exome

AF:

0.000211

Gnomad4 AMR exome

AF:

0.000505

Gnomad4 ASJ exome

AF:

0.00795

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000460

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000261

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.000827

AC:

126

AN:

152352

Hom.:

Cov.:

AF XY:

0.000980

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00952

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000821

Hom.:

Bravo

AF:

0.000910

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000577

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 20, 2021

The c.887T>C (p.I296T) alteration is located in exon 7 (coding exon 6) of the TMEM117 gene. This alteration results from a T to C substitution at nucleotide position 887, causing the isoleucine (I) at amino acid position 296 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

Pathogenic

0.95

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

-0.060

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.15

T;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.037

MetaRNN

Benign

0.0091

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-3.6

D;.

REVEL

Uncertain

0.33

Sift

Uncertain

0.0030

D;.

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.56

P;.

Vest4

0.84

MVP

0.42

MPC

0.71

ClinPred

0.088

GERP RS

5.4

Varity_R

0.51

gMVP

0.98

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