Variant chr7-112783740-A-C 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_022484.6(TMEM168):c.1086T>G(p.Phe362Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000057 in 1,402,834 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: not found (cov: 32)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

TMEM168
NM_022484.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.173

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 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=0.14104396).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM168	NM_022484.6 linkuse as main transcript	c.1086T>G	p.Phe362Leu	missense_variant	2/5	ENST00000312814.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM168	ENST00000312814.11 linkuse as main transcript	c.1086T>G	p.Phe362Leu	missense_variant	2/5	1	NM_022484.6	P1	Q9H0V1-1
LINC03076	ENST00000656697.1 linkuse as main transcript	n.469-112613A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000142

AC:

AN:

211786

Hom.:

AF XY:

0.00000869

AC XY:

AN XY:

115062

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:

0.0000294

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000570

AC:

AN:

1402834

Hom.:

Cov.:

AF XY:

0.00000577

AC XY:

AN XY:

692672

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:

0.00000736

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

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 28, 2023

The c.1086T>G (p.F362L) alteration is located in exon 2 (coding exon 1) of the TMEM168 gene. This alteration results from a T to G substitution at nucleotide position 1086, causing the phenylalanine (F) at amino acid position 362 to be replaced by a leucine (L). 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

0.78

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.32

CADD

Benign

9.5

DANN

Benign

0.85

DEOGEN2

Benign

0.22

T;T;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.80

.;T;T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-2.6

D;D;D;D

REVEL

Benign

0.26

Sift

Benign

0.22

T;T;D;T

Sift4G

Pathogenic

0.0

D;D;D;.

Polyphen

0.0020

B;B;.;.

Vest4

0.48

MutPred

0.46

Loss of catalytic residue at F362 (P = 0.1699);Loss of catalytic residue at F362 (P = 0.1699);.;.;

MVP

0.11

MPC

0.14

ClinPred

0.11

GERP RS

-7.0

Varity_R

0.43

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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