11-58838300-C-G

Variant names:

• chr11-58838300-C-G
• NM_145016.4:c.147G>C

Variant summary

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

The NM_145016.4(GLYATL2):​c.147G>C​(p.Trp49Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GLYATL2 NM_145016.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.27

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, 0.97

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLYATL2	NM_145016.4	c.147G>C	p.Trp49Cys	missense_variant	Exon 3 of 6	ENST00000287275.6	NP_659453.3
GLYATL2	XM_017017337.3	c.147G>C	p.Trp49Cys	missense_variant	Exon 4 of 7		XP_016872826.1
GLYATL2	XM_017017338.3	c.147G>C	p.Trp49Cys	missense_variant	Exon 3 of 6		XP_016872827.1
GLYATL2	XM_047426545.1	c.24G>C	p.Trp8Cys	missense_variant	Exon 2 of 5		XP_047282501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLYATL2	ENST00000287275.6	c.147G>C	p.Trp49Cys	missense_variant	Exon 3 of 6	1	NM_145016.4	ENSP00000287275.1
GLYATL2	ENST00000532258.1	c.147G>C	p.Trp49Cys	missense_variant	Exon 4 of 7	1		ENSP00000434277.1
GLYATL2	ENST00000533636.1	n.129G>C		non_coding_transcript_exon_variant	Exon 2 of 5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461074 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726868

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.147G>C (p.W49C) alteration is located in exon 3 (coding exon 2) of the GLYATL2 gene. This alteration results from a G to C substitution at nucleotide position 147, causing the tryptophan (W) at amino acid position 49 to be replaced by a cysteine (C). 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	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.88	.;D
M_CAP	Benign	0.018	T
MetaRNN	Pathogenic	0.97	D;D
MetaSVM	Benign	-0.61	T
MutationAssessor	Pathogenic	3.3	M;M
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-13	D;D
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.64
MutPred		0.88		Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);
MVP		0.58
MPC		0.16
ClinPred		1.0	D
GERP RS		3.6
Varity_R		0.78
gMVP		0.67

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: chr11-58605773;