NM_145016.4:c.849G>C

Variant names:

• chr11-58834465-C-G
• rs1853388596
• NM_145016.4:c.849G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_145016.4(GLYATL2):​c.849G>C​(p.Trp283Cys) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GLYATL2 NM_145016.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.87

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.875

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLYATL2	NM_145016.4	c.849G>C	p.Trp283Cys	missense_variant	Exon 6 of 6	ENST00000287275.6	NP_659453.3
GLYATL2	XM_017017337.3	c.849G>C	p.Trp283Cys	missense_variant	Exon 7 of 7		XP_016872826.1
GLYATL2	XM_017017338.3	c.849G>C	p.Trp283Cys	missense_variant	Exon 6 of 6		XP_016872827.1
GLYATL2	XM_047426545.1	c.726G>C	p.Trp242Cys	missense_variant	Exon 5 of 5		XP_047282501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLYATL2	ENST00000287275.6	c.849G>C	p.Trp283Cys	missense_variant	Exon 6 of 6	1	NM_145016.4	ENSP00000287275.1
GLYATL2	ENST00000532258.1	c.849G>C	p.Trp283Cys	missense_variant	Exon 7 of 7	1		ENSP00000434277.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.098	T;T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.65	.;T
M_CAP	Benign	0.0051	T
MetaRNN	Pathogenic	0.88	D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Pathogenic	3.1	M;M
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-11	D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.50
MutPred		0.85		Loss of ubiquitination at K287 (P = 0.0508);Loss of ubiquitination at K287 (P = 0.0508);
MVP		0.51
MPC		0.16
ClinPred		1.0	D
GERP RS		4.1
Varity_R		0.59
gMVP		0.51

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: rs1853388596; hg19: chr11-58601938;