Variant chr8-142727839-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000336138.4(THEM6):c.493C>G(p.Gln165Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000968 in 1,445,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000077 ( 0 hom. )

Consequence

THEM6
ENST00000336138.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40

Variant links:

Genes affected

THEM6 (HGNC:29656): (thioesterase superfamily member 6) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

THEM6 links:

THEM6 (HGNC:):

THEM6 links:

Genome browser will be placed here

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=0.06733912).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THEM6	NM_016647.3 linkuse as main transcript	c.493C>G	p.Gln165Glu	missense_variant	1/2	ENST00000336138.4	NP_057731.1	Q8WUY1
THEM6	NM_001363000.2 linkuse as main transcript	c.354+139C>G		intron_variant			NP_001349929.1
THEM6	NR_156431.2 linkuse as main transcript	n.617C>G		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THEM6	ENST00000336138.4 linkuse as main transcript	c.493C>G	p.Gln165Glu	missense_variant	1/2	1	NM_016647.3	ENSP00000338607.3		Q8WUY1
THEM6	ENST00000520217.1 linkuse as main transcript	n.115C>G		non_coding_transcript_exon_variant	1/3	3		ENSP00000427970.1		H0YAR9

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000773

AC:

AN:

1293382

Hom.:

Cov.:

AF XY:

0.00000474

AC XY:

AN XY:

633568

show subpopulations

Gnomad4 AFR exome

AF:

0.000231

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.62e-7

Gnomad4 OTH exome

AF:

0.0000186

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000793

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 20, 2024

The c.493C>G (p.Q165E) alteration is located in exon 1 (coding exon 1) of the THEM6 gene. This alteration results from a C to G substitution at nucleotide position 493, causing the glutamine (Q) at amino acid position 165 to be replaced by a glutamic acid (E). 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

0.082

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.52

DEOGEN2

Benign

0.0064

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.61

M_CAP

Benign

0.0081

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.16

MutationTaster

Benign

0.94

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.34

REVEL

Benign

0.068

Sift

Benign

0.72

Sift4G

Benign

0.79

Polyphen

0.019

Vest4

0.045

MutPred

0.38

Gain of disorder (P = 0.1465);

MVP

0.048

MPC

0.96

ClinPred

0.091

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.22

gMVP

0.28

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