Genetic Variant GLYATL1:p.Val74Ile (chr11-58954803-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001389712.2(GLYATL1):c.220G>A(p.Val74Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,610,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

GLYATL1
NM_001389712.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00400

Variant links:

Genes affected

GLYATL1 (HGNC:30519): (glycine-N-acyltransferase like 1) Enables glutamine N-acyltransferase activity. Involved in glutamine metabolic process. Predicted to be located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

GLYATL1 links:

ENSG00000255240 (HGNC:58086):

ENSG00000255240 links:

LOC283194 (HGNC:):

LOC283194 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37850645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLYATL1	NM_001389712.2 link	c.220G>A	p.Val74Ile	missense_variant	Exon 5 of 7	ENST00000532726.6	NP_001376641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLYATL1	ENST00000532726.6 link	c.220G>A	p.Val74Ile	missense_variant	Exon 5 of 7	3	NM_001389712.2	ENSP00000436116.2		Q969I3-1E9PR27

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000478

GnomAD3 exomes

AF:

0.0000642

AC:

AN:

249072

Hom.:

AF XY:

0.0000966

AC XY:

AN XY:

134574

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000585

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000234

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000322

AC:

AN:

1458548

Hom.:

Cov.:

AF XY:

0.0000386

AC XY:

AN XY:

725596

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.0000906

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000222

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.000478

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.00

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

Mar 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.313G>A (p.V105I) alteration is located in exon 5 (coding exon 5) of the GLYATL1 gene. This alteration results from a G to A substitution at nucleotide position 313, causing the valine (V) at amino acid position 105 to be replaced by an isoleucine (I). 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

0.090

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.42

DANN

Benign

0.85

DEOGEN2

Benign

0.061

.;T;T;.;T

Eigen

Benign

-0.89

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.00057

LIST_S2

Benign

0.16

T;.;T;T;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.38

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.4

.;M;.;.;M

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.88

N;N;N;N;.

REVEL

Benign

0.076

Sift

Benign

0.13

T;D;T;T;.

Sift4G

Uncertain

0.048

D;D;D;D;D

Polyphen

0.76, 0.84

.;P;.;P;P

Vest4

0.037

MutPred

0.70

.;Gain of catalytic residue at V74 (P = 0.1075);Gain of catalytic residue at V74 (P = 0.1075);.;Gain of catalytic residue at V74 (P = 0.1075);

MVP

0.20

MPC

0.049

ClinPred

0.028

GERP RS

-0.34

Varity_R

0.046

gMVP

0.060

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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