Variant 8-142727515-T-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 ENST00000336138.4(THEM6):c.169T>A(p.Ser57Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000317 in 1,579,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 7.0e-7 ( 0 hom. )

Consequence

THEM6
ENST00000336138.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.76

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:

ENSG00000253806 (HGNC:):

ENSG00000253806 links:

Genome browser will be placed here

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=0.07356909).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THEM6	NM_016647.3 linkuse as main transcript	c.169T>A	p.Ser57Thr	missense_variant	1/2	ENST00000336138.4	NP_057731.1	Q8WUY1
THEM6	NM_001363000.2 linkuse as main transcript	c.169T>A	p.Ser57Thr	missense_variant	1/2		NP_001349929.1
THEM6	NR_156431.2 linkuse as main transcript	n.293T>A		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.169T>A	p.Ser57Thr	missense_variant	1/2	1	NM_016647.3	ENSP00000338607.3		Q8WUY1
ENSG00000253806	ENST00000519782.1 linkuse as main transcript	n.108A>T		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

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:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.01e-7

AC:

AN:

1427428

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

709632

show subpopulations

Gnomad4 AFR exome

AF:

0.0000322

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152050

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.0000966

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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000302

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

Dec 27, 2023

The c.169T>A (p.S57T) alteration is located in exon 1 (coding exon 1) of the THEM6 gene. This alteration results from a T to A substitution at nucleotide position 169, causing the serine (S) at amino acid position 57 to be replaced by a threonine (T). 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

0.14

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0048

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.81

M_CAP

Uncertain

0.090

MetaRNN

Benign

0.074

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.26

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-0.62

REVEL

Benign

0.086

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.14

Vest4

0.16

MutPred

0.36

Loss of methylation at R53 (P = 0.1568);

MVP

0.16

MPC

1.1

ClinPred

0.67

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.16

gMVP

0.75

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