11-58955624-T-A

Position:

• chr11-58955624-T-A

Variant summary

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

The NM_001389712.2(GLYATL1):​c.506T>A​(p.Phe169Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,278 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: GLYATL1 NM_001389712.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.300

Genes affected

GLYATL1 (HGNC:30519): (glycine-N-acyltransferase like 1) Enables glutamine N-acyltransferase activity. Involved in glutamine metabolic process. Predicted to be located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

GLYATL1 (HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
GLYATL1	NM_001389712.2	c.506T>A	p.Phe169Tyr	missense_variant	7/7	ENST00000532726.6	NP_001376641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLYATL1	ENST00000532726.6	c.506T>A	p.Phe169Tyr	missense_variant	7/7	3	NM_001389712.2	ENSP00000436116.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251050 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135680

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000869

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461278 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726892

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000895

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 05, 2022

The c.599T>A (p.F200Y) alteration is located in exon 7 (coding exon 7) of the GLYATL1 gene. This alteration results from a T to A substitution at nucleotide position 599, causing the phenylalanine (F) at amino acid position 200 to be replaced by a tyrosine (Y). 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	0.15
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;.;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.0097	N
LIST_S2	Benign	0.50	.;T;T
M_CAP	Benign	0.00064	T
MetaRNN	Uncertain	0.56	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.3	M;.;M
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.5	D;D;.
REVEL	Benign	0.13
Sift	Uncertain	0.0090	D;D;.
Sift4G	Uncertain	0.020	D;T;D
Polyphen		0.87	P;P;P
Vest4		0.26
MutPred		0.82		Loss of catalytic residue at F169 (P = 0.0138);.;Loss of catalytic residue at F169 (P = 0.0138);
MVP		0.21
MPC		0.38
ClinPred		0.82	D
GERP RS		1.6
Varity_R		0.26
gMVP		0.19

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: rs753908233; hg19: chr11-58723097;