6-49515750-G-A

Variant names:

• chr6-49515750-G-A
• rs1018824721
• NM_001010904.2:c.176G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001010904.2(GLYATL3):​c.176G>A​(p.Arg59Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 1,384,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: GLYATL3 NM_001010904.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.985

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]

ACMG classification

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=0.3004192).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLYATL3	NM_001010904.2	c.176G>A	p.Arg59Gln	missense_variant	Exon 3 of 6	ENST00000371197.9	NP_001010904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLYATL3	ENST00000371197.9	c.176G>A	p.Arg59Gln	missense_variant	Exon 3 of 6	2	NM_001010904.2	ENSP00000360240.4
GLYATL3	ENST00000545705.1	c.176G>A	p.Arg59Gln	missense_variant	Exon 3 of 6	5		ENSP00000440029.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000217 AC: 3 AN: 1384730 Hom.: 0 Cov.: 26 AF XY: 0.00000146 AC XY: 1 AN XY: 684008

Gnomad4 AFR exome AF: 0.0000319

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: 0.00000188

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.176G>A (p.R59Q) alteration is located in exon 3 (coding exon 2) of the GLYATL3 gene. This alteration results from a G to A substitution at nucleotide position 176, causing the arginine (R) at amino acid position 59 to be replaced by a glutamine (Q). 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	0.099
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	22
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.014	T;.
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.21	N;N
REVEL	Benign	0.15
Sift	Benign	0.27	T;D
Sift4G	Benign	0.12	T;T
Polyphen		1.0	D;.
Vest4		0.19
MutPred		0.72		Loss of phosphorylation at T57 (P = 0.1082);Loss of phosphorylation at T57 (P = 0.1082);
MVP		0.030
ClinPred		0.91	D
GERP RS		4.4
Varity_R		0.056
gMVP		0.45

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

Other links and lift over

dbSNP: rs1018824721; hg19: chr6-49483463;