Variant chr7-112767447-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022484.6(TMEM168):c.1844T>A(p.Val615Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000106 in 1,614,076 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: 𝑓 0.00046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000069 ( 0 hom. )

Consequence

TMEM168
NM_022484.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.21

Variant links:

Genes affected

TMEM168 (HGNC:25826): (transmembrane protein 168) Located in transport vesicle. [provided by Alliance of Genome Resources, Apr 2022]

TMEM168 links:

LINC03076 (HGNC:56656): (long intergenic non-protein coding RNA 3076)

LINC03076 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.018059224).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM168	NM_022484.6 linkuse as main transcript	c.1844T>A	p.Val615Glu	missense_variant	5/5	ENST00000312814.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM168	ENST00000312814.11 linkuse as main transcript	c.1844T>A	p.Val615Glu	missense_variant	5/5	1	NM_022484.6	P1	Q9H0V1-1
LINC03076	ENST00000656697.1 linkuse as main transcript	n.469-128906A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

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:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000155

AC:

AN:

251146

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135720

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.0000579

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:

0.00000881

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.0000691

AC:

101

AN:

1461866

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00251

Gnomad4 AMR exome

AF:

0.0000894

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:

0.00000180

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000460

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00164

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000630

Hom.:

Bravo

AF:

0.000582

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000189

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

Jun 16, 2023

The c.1844T>A (p.V615E) alteration is located in exon 5 (coding exon 4) of the TMEM168 gene. This alteration results from a T to A substitution at nucleotide position 1844, causing the valine (V) at amino acid position 615 to be replaced by a glutamic acid (E). 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

0.27

BayesDel_addAF

Benign

-0.039

BayesDel_noAF

Pathogenic

0.16

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.21

T;T;.;T

Eigen

Benign

-0.097

Eigen_PC

Benign

-0.070

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.86

.;D;D;D

M_CAP

Benign

0.0043

MetaRNN

Benign

0.018

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.8

L;L;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-4.0

D;D;D;D

REVEL

Benign

0.20

Sift

Uncertain

0.011

D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

0.51

P;P;.;.

Vest4

0.59

MVP

0.19

MPC

0.23

ClinPred

0.042

GERP RS

5.7

Varity_R

0.63

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