Genetic Variant GLYATL2:p.Gln62Arg (chr11-58838262-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_145016.4(GLYATL2):c.185A>G(p.Gln62Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000312 in 1,600,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

GLYATL2
NM_145016.4 missense, splice_region

Scores

Splicing: ADA: 0.9804

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.31

Variant links:

Genes affected

GLYATL2 (HGNC:24178): (glycine-N-acyltransferase like 2) Enables glycine N-acyltransferase activity. Involved in long-chain fatty acid catabolic process; medium-chain fatty acid catabolic process; and monounsaturated fatty acid catabolic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

GLYATL2 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 rank	MANE	Protein	UniProt
GLYATL2	NM_145016.4 link	c.185A>G	p.Gln62Arg	missense_variant, splice_region_variant	Exon 3 of 6	ENST00000287275.6	NP_659453.3	Q8WU03A0A024R4Z5
GLYATL2	XM_017017337.3 link	c.185A>G	p.Gln62Arg	missense_variant, splice_region_variant	Exon 4 of 7		XP_016872826.1	Q8WU03A0A024R4Z5
GLYATL2	XM_017017338.3 link	c.185A>G	p.Gln62Arg	missense_variant, splice_region_variant	Exon 3 of 6		XP_016872827.1	Q8WU03A0A024R4Z5
GLYATL2	XM_047426545.1 link	c.62A>G	p.Gln21Arg	missense_variant, splice_region_variant	Exon 2 of 5		XP_047282501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GLYATL2	ENST00000287275.6 link	c.185A>G	p.Gln62Arg	missense_variant, splice_region_variant	Exon 3 of 6	1	NM_145016.4	ENSP00000287275.1	Q8WU03
GLYATL2	ENST00000532258.1 link	c.185A>G	p.Gln62Arg	missense_variant, splice_region_variant	Exon 4 of 7	1		ENSP00000434277.1	Q8WU03
GLYATL2	ENST00000533636.1 link	n.167A>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 5	3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152144

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

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1448842

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

721758

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:

0.00000273

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74312

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

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

Nov 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.185A>G (p.Q62R) alteration is located in exon 3 (coding exon 2) of the GLYATL2 gene. This alteration results from a A to G substitution at nucleotide position 185, causing the glutamine (Q) at amino acid position 62 to be replaced by an arginine (R). 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

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.031

T;T

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.36

.;T

M_CAP

Benign

0.0074

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

M;M

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.1

D;D

REVEL

Benign

0.10

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

0.44

B;B

Vest4

0.17

MutPred

0.70

Loss of ubiquitination at K61 (P = 0.0481);Loss of ubiquitination at K61 (P = 0.0481);

MVP

0.38

MPC

0.018

ClinPred

0.87

GERP RS

3.6

Varity_R

0.47

gMVP

0.049

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.98

dbscSNV1_RF

Pathogenic

0.87

SpliceAI score (max)

0.030

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