rs750660285

Variant names:

• chr11-58837379-C-A
• rs750660285
• NM_145016.4:c.205G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-58837379-C-A
• chr11-58837379-C-T

Variant summary

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

The NM_145016.4(GLYATL2):​c.205G>T​(p.Asp69Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,846 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: GLYATL2 NM_145016.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88

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, 0.96

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLYATL2	NM_145016.4	c.205G>T	p.Asp69Tyr	missense_variant	Exon 4 of 6	ENST00000287275.6	NP_659453.3
GLYATL2	XM_017017337.3	c.205G>T	p.Asp69Tyr	missense_variant	Exon 5 of 7		XP_016872826.1
GLYATL2	XM_017017338.3	c.205G>T	p.Asp69Tyr	missense_variant	Exon 4 of 6		XP_016872827.1
GLYATL2	XM_047426545.1	c.82G>T	p.Asp28Tyr	missense_variant	Exon 3 of 5		XP_047282501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLYATL2	ENST00000287275.6	c.205G>T	p.Asp69Tyr	missense_variant	Exon 4 of 6	1	NM_145016.4	ENSP00000287275.1
GLYATL2	ENST00000532258.1	c.205G>T	p.Asp69Tyr	missense_variant	Exon 5 of 7	1		ENSP00000434277.1
GLYATL2	ENST00000533636.1	n.187G>T		non_coding_transcript_exon_variant	Exon 3 of 5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 249010 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135102

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460846 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726774

Gnomad4 AFR exome AF: 0.00

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: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.85	.;T
M_CAP	Benign	0.0040	T
MetaRNN	Pathogenic	0.96	D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Pathogenic	3.3	M;M
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-8.8	D;D
REVEL	Benign	0.27
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.65
MutPred		0.85		Loss of disorder (P = 0.0294);Loss of disorder (P = 0.0294);
MVP		0.50
MPC		0.15
ClinPred		0.87	D
GERP RS		3.3
Varity_R		0.50
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs750660285; hg19: chr11-58604852;