Genetic Variant GLYATL3:p.Asn166Asp (chr6-49526543-A-G) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

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

The NM_001010904.2(GLYATL3):c.496A>G(p.Asn166Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000477 in 1,551,654 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 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

GLYATL3
NM_001010904.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.47

Variant links:

Genes affected

GLYATL3 (HGNC:21349): (glycine-N-acyltransferase like 3) Predicted to enable glycine N-acyltransferase activity. Predicted to be located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

GLYATL3 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, 0.959

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLYATL3	NM_001010904.2 link	c.496A>G	p.Asn166Asp	missense_variant	Exon 6 of 6	ENST00000371197.9	NP_001010904.1	Q5SZD4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLYATL3	ENST00000371197.9 link	c.496A>G	p.Asn166Asp	missense_variant	Exon 6 of 6	2	NM_001010904.2	ENSP00000360240.4		Q5SZD4
GLYATL3	ENST00000545705.1 link	c.*28A>G		downstream_gene_variant		5		ENSP00000440029.1		F5GXQ5

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000637

AC:

AN:

157058

Hom.:

AF XY:

0.0000120

AC XY:

AN XY:

83108

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:

0.0000164

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000472

AC:

AN:

1399480

Hom.:

Cov.:

AF XY:

0.0000435

AC XY:

AN XY:

690224

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:

0.0000556

Gnomad4 OTH exome

AF:

0.000103

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000116

Hom.:

Bravo

AF:

0.0000453

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 19, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.496A>G (p.N166D) alteration is located in exon 6 (coding exon 5) of the GLYATL3 gene. This alteration results from a A to G substitution at nucleotide position 496, causing the asparagine (N) at amino acid position 166 to be replaced by an aspartic acid (D). 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

0.30

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.078

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.72

M_CAP

Benign

0.0078

MetaRNN

Pathogenic

0.96

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-4.4

REVEL

Uncertain

0.43

Sift

Benign

0.094

Sift4G

Benign

0.081

Polyphen

0.99

Vest4

0.58

MutPred

0.93

Loss of MoRF binding (P = 0.0876);

MVP

0.067

ClinPred

0.99

GERP RS

6.1

Varity_R

0.47

gMVP

0.87

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