11-58955824-G-C

Position:

• chr11-58955824-G-C

Variant summary

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

The NM_001389712.2(GLYATL1):​c.706G>C​(p.Glu236Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GLYATL1 NM_001389712.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.265

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29455107).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLYATL1	NM_001389712.2	c.706G>C	p.Glu236Gln	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.706G>C	p.Glu236Gln	missense_variant	7/7	3	NM_001389712.2	ENSP00000436116.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Nov 09, 2021

The c.799G>C (p.E267Q) alteration is located in exon 7 (coding exon 7) of the GLYATL1 gene. This alteration results from a G to C substitution at nucleotide position 799, causing the glutamic acid (E) at amino acid position 267 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	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T;.;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.0017	N
LIST_S2	Benign	0.64	.;T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.;L
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.54	N;N;.
REVEL	Benign	0.067
Sift	Uncertain	0.0060	D;D;.
Sift4G	Uncertain	0.017	D;T;D
Polyphen		0.99	D;D;D
Vest4		0.061
MutPred		0.69		Loss of ubiquitination at K237 (P = 0.0352);.;Loss of ubiquitination at K237 (P = 0.0352);
MVP		0.44
MPC		0.30
ClinPred		0.41	T
GERP RS		-0.38
Varity_R		0.10
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-58723297;