Variant 7-112767642-G-C 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.1649C>G(p.Thr550Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

TMEM168
NM_022484.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.863

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:

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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=0.033531755).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM168	NM_022484.6 linkuse as main transcript	c.1649C>G	p.Thr550Ser	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.1649C>G	p.Thr550Ser	missense_variant	5/5	1	NM_022484.6	P1	Q9H0V1-1
LINC03076	ENST00000656697.1 linkuse as main transcript	n.469-128711G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251096

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135734

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:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461828

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727214

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:

0.00000540

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Apr 05, 2023

The c.1649C>G (p.T550S) alteration is located in exon 5 (coding exon 4) of the TMEM168 gene. This alteration results from a C to G substitution at nucleotide position 1649, causing the threonine (T) at amino acid position 550 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

0.072

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.016

T;T;.;T

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.70

.;T;T;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.034

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

N;N;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.36

N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.89

T;T;T;T

Sift4G

Benign

0.16

T;T;T;T

Polyphen

0.0

B;B;.;.

Vest4

0.085

MutPred

0.23

Gain of disorder (P = 0.0239);Gain of disorder (P = 0.0239);.;.;

MVP

0.29

MPC

0.094

ClinPred

0.016

GERP RS

3.7

Varity_R

0.029

gMVP

0.17

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