Variant chr11-58712781-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_201648.3(GLYAT):c.295A>G(p.Lys99Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GLYAT
NM_201648.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.57

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.819

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLYAT	NM_201648.3 linkuse as main transcript	c.295A>G	p.Lys99Glu	missense_variant	4/6	ENST00000344743.8	NP_964011.2	Q6IB77-1A0A384P5E3
GLYAT	NM_005838.4 linkuse as main transcript	c.295A>G	p.Lys99Glu	missense_variant	4/5		NP_005829.3	Q6IB77-2
GLYAT	XM_017017087.1 linkuse as main transcript	c.103A>G	p.Lys35Glu	missense_variant	4/6		XP_016872576.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLYAT	ENST00000344743.8 linkuse as main transcript	c.295A>G	p.Lys99Glu	missense_variant	4/6	1	NM_201648.3	ENSP00000340200.3		Q6IB77-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460872

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726814

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.:

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 07, 2024

The c.295A>G (p.K99E) alteration is located in exon 4 (coding exon 3) of the GLYAT gene. This alteration results from a A to G substitution at nucleotide position 295, causing the lysine (K) at amino acid position 99 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

0.14

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T;T;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.74

T;.;.;T

M_CAP

Benign

0.014

MetaRNN

Pathogenic

0.82

D;D;D;D

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.6

M;M;M;M

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-3.5

.;D;D;D

REVEL

Benign

0.27

Sift

Benign

0.24

.;T;T;T

Sift4G

Benign

0.32

T;T;T;T

Polyphen

1.0

D;D;D;D

Vest4

0.59

MutPred

0.62

Loss of methylation at K99 (P = 0.0039);Loss of methylation at K99 (P = 0.0039);Loss of methylation at K99 (P = 0.0039);Loss of methylation at K99 (P = 0.0039);

MVP

0.51

MPC

0.14

ClinPred

0.98

GERP RS

5.8

Varity_R

0.44

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over