Variant 11-58834600-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000287275.6(GLYATL2):c.714G>A(p.Met238Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GLYATL2
ENST00000287275.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.227

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05416572).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GLYATL2	NM_145016.4 linkuse as main transcript	c.714G>A	p.Met238Ile	missense_variant	6/6	ENST00000287275.6	NP_659453.3
GLYATL2	XM_017017337.3 linkuse as main transcript	c.714G>A	p.Met238Ile	missense_variant	7/7		XP_016872826.1
GLYATL2	XM_017017338.3 linkuse as main transcript	c.714G>A	p.Met238Ile	missense_variant	6/6		XP_016872827.1
GLYATL2	XM_047426545.1 linkuse as main transcript	c.591G>A	p.Met197Ile	missense_variant	5/5		XP_047282501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLYATL2	ENST00000287275.6 linkuse as main transcript	c.714G>A	p.Met238Ile	missense_variant	6/6	1	NM_145016.4	ENSP00000287275	P1
GLYATL2	ENST00000532258.1 linkuse as main transcript	c.714G>A	p.Met238Ile	missense_variant	7/7	1		ENSP00000434277	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461506

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727064

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Jan 23, 2024

The c.714G>A (p.M238I) alteration is located in exon 6 (coding exon 5) of the GLYATL2 gene. This alteration results from a G to A substitution at nucleotide position 714, causing the methionine (M) at amino acid position 238 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

Uncertain

0.47

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.0

DANN

Benign

0.64

DEOGEN2

Benign

0.0030

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.46

.;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.054

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.79

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.62

N;N

REVEL

Benign

0.016

Sift

Benign

0.94

T;T

Sift4G

Benign

0.51

T;T

Polyphen

0.022

B;B

Vest4

0.12

MutPred

0.32

Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);

MVP

0.14

MPC

0.14

ClinPred

0.069

GERP RS

-3.2

Varity_R

0.079

gMVP

0.43

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