Variant 11-58709944-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_201648.3(GLYAT):c.713G>A(p.Arg238Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000576 in 1,613,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

GLYAT
NM_201648.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.13

Variant links:

Genes affected

GLYAT (HGNC:13734): (glycine-N-acyltransferase) The glycine-N-acyltransferase protein conjugates glycine with acyl-CoA substrates in the mitochondria. The protein is thought to be important in the detoxification of endogenous and xenobiotic acyl-CoA's. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GLYAT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.877

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLYAT	NM_201648.3 linkuse as main transcript	c.713G>A	p.Arg238Gln	missense_variant	6/6	ENST00000344743.8	NP_964011.2	Q6IB77-1A0A384P5E3
GLYAT	XM_017017087.1 linkuse as main transcript	c.521G>A	p.Arg174Gln	missense_variant	6/6		XP_016872576.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GLYAT	ENST00000344743.8 linkuse as main transcript	c.713G>A	p.Arg238Gln	missense_variant	6/6	1	NM_201648.3	ENSP00000340200.3	Q6IB77-1
GLYAT	ENST00000529732.5 linkuse as main transcript	c.713G>A	p.Arg238Gln	missense_variant	6/6	5		ENSP00000431688.1	Q6IB77-1
GLYAT	ENST00000611865.4 linkuse as main transcript	c.713G>A	p.Arg238Gln	missense_variant	5/5	3		ENSP00000484592.1	Q6IB77-1
GLYAT	ENST00000586098.1 linkuse as main transcript	c.88+2816G>A		intron_variant		3		ENSP00000468512.1	K7ES21

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000837

AC:

AN:

250912

Hom.:

AF XY:

0.0000737

AC XY:

AN XY:

135622

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.000894

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.0000575

AC:

AN:

1461692

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00111

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000987

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Aug 02, 2022

The c.713G>A (p.R238Q) alteration is located in exon 6 (coding exon 5) of the GLYAT gene. This alteration results from a G to A substitution at nucleotide position 713, causing the arginine (R) at amino acid position 238 to be replaced by a glutamine (Q). 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

-0.27

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.41

T;T;T

Eigen

Benign

0.12

Eigen_PC

Benign

0.033

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.85

T;.;.

M_CAP

Benign

0.017

MetaRNN

Pathogenic

0.88

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

M;M;M

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-2.6

.;D;D

REVEL

Benign

0.28

Sift

Benign

0.046

.;D;D

Sift4G

Uncertain

0.054

T;T;T

Polyphen

0.98

D;D;D

Vest4

0.34

MutPred

0.95

Loss of methylation at R238 (P = 0.0358);Loss of methylation at R238 (P = 0.0358);Loss of methylation at R238 (P = 0.0358);

MVP

0.41

MPC

0.062

ClinPred

0.12

GERP RS

4.1

Varity_R

0.10

gMVP

0.82

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