Variant 8-55756394-T-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_001286657.2(TMEM68):c.343A>G(p.Met115Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,914 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: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

TMEM68
NM_001286657.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.718

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:

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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=0.1722945).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM68	NM_001286657.2 linkuse as main transcript	c.343A>G	p.Met115Val	missense_variant	4/8	ENST00000434581.7	NP_001273586.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM68	ENST00000434581.7 linkuse as main transcript	c.343A>G	p.Met115Val	missense_variant	4/8	5	NM_001286657.2	ENSP00000395204	P1	Q96MH6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.00e-7

AC:

AN:

1428914

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

710008

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:

9.07e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 16, 2024

The c.343A>G (p.M115V) alteration is located in exon 4 (coding exon 2) of the TMEM68 gene. This alteration results from a A to G substitution at nucleotide position 343, causing the methionine (M) at amino acid position 115 to be replaced by a valine (V). 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

0.099

BayesDel_addAF

Uncertain

0.056

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.26

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

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.58

LIST_S2

Uncertain

0.87

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

M_CAP

Benign

0.063

MetaRNN

Benign

0.10

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

MetaSVM

Uncertain

-0.27

MutationAssessor

Benign

-0.18

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

MutationTaster

Benign

1.0

D;D;N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.65

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

REVEL

Benign

0.29

Sift

Benign

0.43

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

Sift4G

Benign

0.58

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

Polyphen

0.0010

B;B;B;.;.;.;.;.;.

Vest4

0.17

MutPred

0.35

Loss of disorder (P = 0.1303);Loss of disorder (P = 0.1303);Loss of disorder (P = 0.1303);.;.;.;Loss of disorder (P = 0.1303);Loss of disorder (P = 0.1303);Loss of disorder (P = 0.1303);

MVP

0.41

MPC

0.42

ClinPred

0.16

GERP RS

3.1

Varity_R

0.042

gMVP

0.80

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over