11-58709968-A-C

Variant names:

• chr11-58709968-A-C
• NM_201648.3:c.689T>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_201648.3(GLYAT):​c.689T>G​(p.Met230Arg) 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: GLYAT NM_201648.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.78
• Publications: 0 publications found

Genes affected

GLYAT (HGNC:13734): (glycine-N-acyltransferase) The glycine-N-acyltransferase protein conjugates glycine with acyl-CoA substrates in the mitochondria. The protein is thought to be important in the detoxification of endogenous and xenobiotic acyl-CoA's. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.978

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201648.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLYAT	NM_201648.3	MANE Select	c.689T>G	p.Met230Arg	missense	Exon 6 of 6	NP_964011.2	A0A384P5E3
	GLYAT	NM_005838.4		c.*618T>G		downstream_gene	N/A	NP_005829.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLYAT	ENST00000344743.8	TSL:1 MANE Select	c.689T>G	p.Met230Arg	missense	Exon 6 of 6	ENSP00000340200.3	Q6IB77-1
	GLYAT	ENST00000529732.5	TSL:5	c.689T>G	p.Met230Arg	missense	Exon 6 of 6	ENSP00000431688.1	Q6IB77-1
	GLYAT	ENST00000611865.4	TSL:3	c.689T>G	p.Met230Arg	missense	Exon 5 of 5	ENSP00000484592.1	Q6IB77-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.46	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.98	D
MetaSVM	Benign	-0.76	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		1.8
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.029	D
Polyphen		0.99	D
Vest4		0.71
MutPred		0.91		Gain of disorder (P = 0.0399)
MVP		0.45
MPC		0.15
ClinPred		0.97	D
GERP RS		6.1
Varity_R		0.77
gMVP		0.90
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

hg19: chr11-58477441;