Variant 11-58709960-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_201648.3(GLYAT):c.697A>C(p.Thr233Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000161 in 1,613,914 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 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

GLYAT
NM_201648.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82

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 Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.983

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLYAT	NM_201648.3 linkuse as main transcript	c.697A>C	p.Thr233Pro	missense_variant	6/6	ENST00000344743.8	NP_964011.2	Q6IB77-1A0A384P5E3
GLYAT	XM_017017087.1 linkuse as main transcript	c.505A>C	p.Thr169Pro	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.697A>C	p.Thr233Pro	missense_variant	6/6	1	NM_201648.3	ENSP00000340200.3	Q6IB77-1
GLYAT	ENST00000529732.5 linkuse as main transcript	c.697A>C	p.Thr233Pro	missense_variant	6/6	5		ENSP00000431688.1	Q6IB77-1
GLYAT	ENST00000611865.4 linkuse as main transcript	c.697A>C	p.Thr233Pro	missense_variant	5/5	3		ENSP00000484592.1	Q6IB77-1
GLYAT	ENST00000586098.1 linkuse as main transcript	c.88+2800A>C		intron_variant		3		ENSP00000468512.1	K7ES21

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152226

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250902

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135620

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1461688

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727148

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:

0.0000216

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74384

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:

0.0000294

Gnomad4 OTH

AF:

0.00

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Jun 06, 2023

The c.697A>C (p.T233P) alteration is located in exon 6 (coding exon 5) of the GLYAT gene. This alteration results from a A to C substitution at nucleotide position 697, causing the threonine (T) at amino acid position 233 to be replaced by a proline (P). 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

Pathogenic

0.68

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.64

D;D;D

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.85

T;.;.

M_CAP

Benign

0.050

MetaRNN

Pathogenic

0.98

D;D;D

MetaSVM

Benign

-0.60

MutationAssessor

Pathogenic

3.5

M;M;M

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-5.3

.;D;D

REVEL

Uncertain

0.56

Sift

Uncertain

0.0010

.;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.76

MutPred

0.86

Gain of disorder (P = 0.0663);Gain of disorder (P = 0.0663);Gain of disorder (P = 0.0663);

MVP

0.53

MPC

0.15

ClinPred

0.99

GERP RS

6.1

Varity_R

0.86

gMVP

0.90

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