11-58837162-A-C

Position:

• chr11-58837162-A-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The ENST00000287275.6(GLYATL2):​c.329T>G​(p.Leu110Trp) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GLYATL2 ENST00000287275.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.70

Genes affected

GLYATL2 (HGNC:24178): (glycine-N-acyltransferase like 2) Enables glycine N-acyltransferase activity. Involved in long-chain fatty acid catabolic process; medium-chain fatty acid catabolic process; and monounsaturated fatty acid catabolic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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, 0.965

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLYATL2	NM_145016.4	c.329T>G	p.Leu110Trp	missense_variant	5/6	ENST00000287275.6	NP_659453.3
GLYATL2	XM_017017337.3	c.329T>G	p.Leu110Trp	missense_variant	6/7		XP_016872826.1
GLYATL2	XM_017017338.3	c.329T>G	p.Leu110Trp	missense_variant	5/6		XP_016872827.1
GLYATL2	XM_047426545.1	c.206T>G	p.Leu69Trp	missense_variant	4/5		XP_047282501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLYATL2	ENST00000287275.6	c.329T>G	p.Leu110Trp	missense_variant	5/6	1	NM_145016.4	ENSP00000287275	P1
GLYATL2	ENST00000532258.1	c.329T>G	p.Leu110Trp	missense_variant	6/7	1		ENSP00000434277	P1
GLYATL2	ENST00000533636.1	n.311T>G		non_coding_transcript_exon_variant	4/5	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Dec 16, 2022

The c.329T>G (p.L110W) alteration is located in exon 5 (coding exon 4) of the GLYATL2 gene. This alteration results from a T to G substitution at nucleotide position 329, causing the leucine (L) at amino acid position 110 to be replaced by a tryptophan (W). 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	Uncertain	0.35
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.18	T;T
Eigen	Benign	-0.065
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.69	.;T
M_CAP	Benign	0.0018	T
MetaRNN	Pathogenic	0.97	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.1	M;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-5.9	D;D
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;D
Vest4		0.58
MutPred		0.93		Loss of stability (P = 0.0819);Loss of stability (P = 0.0819);
MVP		0.43
MPC		0.15
ClinPred		0.79	D
GERP RS		3.1
Varity_R		0.31
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr11-58604635;