11-58954798-C-T

Position:

• chr11-58954798-C-T

Variant summary

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

The NM_001389712.2(GLYATL1):​c.215C>T​(p.Thr72Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,130 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: GLYATL1 NM_001389712.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.194

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.215C>T	p.Thr72Ile	missense_variant	5/7	ENST00000532726.6	NP_001376641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLYATL1	ENST00000532726.6	c.215C>T	p.Thr72Ile	missense_variant	5/7	3	NM_001389712.2	ENSP00000436116.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152130 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74322

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

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

Mar 25, 2024

The c.308C>T (p.T103I) alteration is located in exon 5 (coding exon 5) of the GLYATL1 gene. This alteration results from a C to T substitution at nucleotide position 308, causing the threonine (T) at amino acid position 103 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	Benign	0.15
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.13
DANN	Benign	0.91
DEOGEN2	Benign	0.22	.;T;T;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0087	N
LIST_S2	Benign	0.59	T;.;T;T;T
M_CAP	Benign	0.0061	T
MetaRNN	Uncertain	0.63	D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	.;M;.;.;M
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-4.7	D;D;D;D;.
REVEL	Benign	0.092
Sift	Benign	0.032	D;D;T;D;.
Sift4G	Uncertain	0.058	T;T;D;T;T
Polyphen		0.37, 0.17	.;B;.;B;B
Vest4		0.25, 0.25
MutPred		0.82		.;Loss of phosphorylation at T72 (P = 0.0376);Loss of phosphorylation at T72 (P = 0.0376);.;Loss of phosphorylation at T72 (P = 0.0376);
MVP		0.28
MPC		0.18
ClinPred		0.37	T
GERP RS		-1.4
Varity_R		0.12
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs904723937; hg19: chr11-58722271;