Variant 8-55762839-C-A 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_001286657.2(TMEM68):c.121G>T(p.Ala41Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000041 ( 0 hom. )

Consequence

TMEM68
NM_001286657.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0300

Variant links:

Genes affected

TMEM68 (HGNC:26510): (transmembrane protein 68) Predicted to enable acyltransferase activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM68 links:

TMEM68 (HGNC:):

TMEM68 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=0.1347866).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM68	NM_001286657.2 linkuse as main transcript	c.121G>T	p.Ala41Ser	missense_variant	3/8	ENST00000434581.7	NP_001273586.1	Q96MH6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM68	ENST00000434581.7 linkuse as main transcript	c.121G>T	p.Ala41Ser	missense_variant	3/8	5	NM_001286657.2	ENSP00000395204.2		Q96MH6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251204

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461828

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727212

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:

0.00

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

Jun 23, 2023

The c.121G>T (p.A41S) alteration is located in exon 3 (coding exon 1) of the TMEM68 gene. This alteration results from a G to T substitution at nucleotide position 121, causing the alanine (A) at amino acid position 41 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

0.12

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.018

T;T;.;T;T;.;.;.;.

Eigen

Benign

-0.079

Eigen_PC

Benign

0.062

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.90

D;.;D;D;D;D;D;.;D

M_CAP

Benign

0.049

MetaRNN

Benign

0.13

T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.10

MutationAssessor

Benign

0.64

N;N;N;.;.;.;.;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.33

.;N;N;N;N;N;N;N;N

REVEL

Uncertain

0.32

Sift

Benign

0.75

.;T;T;T;T;T;T;T;T

Sift4G

Benign

0.58

T;T;T;.;T;T;.;T;T

Polyphen

0.0

B;B;B;.;.;.;.;P;P

Vest4

0.28

MutPred

0.43

Loss of catalytic residue at A41 (P = 0.0255);Loss of catalytic residue at A41 (P = 0.0255);Loss of catalytic residue at A41 (P = 0.0255);Loss of catalytic residue at A41 (P = 0.0255);Loss of catalytic residue at A41 (P = 0.0255);Loss of catalytic residue at A41 (P = 0.0255);Loss of catalytic residue at A41 (P = 0.0255);Loss of catalytic residue at A41 (P = 0.0255);Loss of catalytic residue at A41 (P = 0.0255);

MVP

0.55

MPC

0.48

ClinPred

0.22

GERP RS

4.3

Varity_R

0.067

gMVP

0.67

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