Variant 8-55751112-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001286657.2(TMEM68):c.539G>A(p.Arg180Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,724 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: 0.0000014 ( 0 hom. )

Consequence

TMEM68
NM_001286657.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.90

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36860242).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM68	NM_001286657.2 linkuse as main transcript	c.539G>A	p.Arg180Lys	missense_variant	5/8	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.539G>A	p.Arg180Lys	missense_variant	5/8	5	NM_001286657.2	ENSP00000395204.2		Q96MH6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

251068

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135718

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461724

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727166

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:

0.00000180

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

Oct 25, 2022

The c.539G>A (p.R180K) alteration is located in exon 5 (coding exon 3) of the TMEM68 gene. This alteration results from a G to A substitution at nucleotide position 539, causing the arginine (R) at amino acid position 180 to be replaced by a lysine (K). 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

0.11

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

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

Eigen

Benign

0.0036

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.86

D;.;D;D;D;D;D;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.37

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

MetaSVM

Uncertain

0.61

MutationAssessor

Benign

1.3

L;L;L;.;.;.;.;.

MutationTaster

Benign

0.76

D;D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.030

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

REVEL

Uncertain

0.47

Sift

Benign

1.0

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

Sift4G

Benign

1.0

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

Polyphen

0.0090

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

Vest4

0.18

MutPred

0.73

Gain of ubiquitination at R180 (P = 0.03);Gain of ubiquitination at R180 (P = 0.03);Gain of ubiquitination at R180 (P = 0.03);.;.;.;Gain of ubiquitination at R180 (P = 0.03);.;

MVP

0.71

MPC

0.43

ClinPred

0.41

GERP RS

5.7

Varity_R

0.080

gMVP

0.67

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