Variant chr1-151848264-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000368817.10(THEM5):c.493A>G(p.Met165Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,944 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

THEM5
ENST00000368817.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.105

Variant links:

Genes affected

THEM5 (HGNC:26755): (thioesterase superfamily member 5) Enables palmitoyl-CoA hydrolase activity. Involved in long-chain fatty-acyl-CoA metabolic process. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

THEM5 links:

C2CD4D-AS1 (HGNC:):

C2CD4D-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THEM5	NM_182578.4 linkuse as main transcript	c.493A>G	p.Met165Val	missense_variant	4/6	ENST00000368817.10	NP_872384.2	Q8N1Q8
THEM5	XM_011509421.2 linkuse as main transcript	c.493A>G	p.Met165Val	missense_variant	4/5		XP_011507723.1
C2CD4D-AS1	NR_024237.2 linkuse as main transcript	n.1031-1969T>C		intron_variant
C2CD4D-AS1	NR_152846.1 linkuse as main transcript	n.951-1969T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
THEM5	ENST00000368817.10 linkuse as main transcript	c.493A>G	p.Met165Val	missense_variant	4/6	1	NM_182578.4	ENSP00000357807.4	Q8N1Q8
THEM5	ENST00000453881.2 linkuse as main transcript	c.139A>G	p.Met47Val	missense_variant	2/3	4		ENSP00000406809.2	H0Y6P4
C2CD4D-AS1	ENST00000434182.1 linkuse as main transcript	n.354-1969T>C		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251082

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

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:

0.00000342

AC:

AN:

1461778

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

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 06, 2021

The c.493A>G (p.M165V) alteration is located in exon 4 (coding exon 4) of the THEM5 gene. This alteration results from a A to G substitution at nucleotide position 493, causing the methionine (M) at amino acid position 165 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

0.13

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.017

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.68

M_CAP

Benign

0.0076

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-0.94

MutationAssessor

Pathogenic

3.0

MutationTaster

Benign

0.95

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.12

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.049

Polyphen

0.13

Vest4

0.63

MutPred

0.50

Loss of disorder (P = 0.0808);

MVP

0.30

MPC

0.14

ClinPred

0.64

GERP RS

-0.76

Varity_R

0.59

gMVP

0.24

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