Genetic Variant GLYATL2:p.Ser96Asn (chr11-58837297-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_145016.4(GLYATL2):c.287G>A(p.Ser96Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,658 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 Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

GLYATL2
NM_145016.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.710

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06187004).

BP6

Variant 11-58837297-C-T is Benign according to our data. Variant chr11-58837297-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3520765.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLYATL2	NM_145016.4 link	c.287G>A	p.Ser96Asn	missense_variant	Exon 4 of 6	ENST00000287275.6	NP_659453.3	Q8WU03A0A024R4Z5
GLYATL2	XM_017017337.3 link	c.287G>A	p.Ser96Asn	missense_variant	Exon 5 of 7		XP_016872826.1	Q8WU03A0A024R4Z5
GLYATL2	XM_017017338.3 link	c.287G>A	p.Ser96Asn	missense_variant	Exon 4 of 6		XP_016872827.1	Q8WU03A0A024R4Z5
GLYATL2	XM_047426545.1 link	c.164G>A	p.Ser55Asn	missense_variant	Exon 3 of 5		XP_047282501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GLYATL2	ENST00000287275.6 link	c.287G>A	p.Ser96Asn	missense_variant	Exon 4 of 6	1	NM_145016.4	ENSP00000287275.1	Q8WU03
GLYATL2	ENST00000532258.1 link	c.287G>A	p.Ser96Asn	missense_variant	Exon 5 of 7	1		ENSP00000434277.1	Q8WU03
GLYATL2	ENST00000533636.1 link	n.269G>A		non_coding_transcript_exon_variant	Exon 3 of 5	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249356

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135274

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:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461658

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000828

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 06, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.74

DANN

Benign

0.28

DEOGEN2

Benign

0.022

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0043

LIST_S2

Benign

0.20

.;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.062

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-3.1

N;N

PrimateAI

Uncertain

0.60

PROVEAN

Benign

4.7

N;N

REVEL

Benign

0.10

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.074

MutPred

0.78

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);

MVP

0.072

MPC

0.017

ClinPred

0.039

GERP RS

3.1

Varity_R

0.025

gMVP

0.043

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