11-58710016-C-A

Position:

• chr11-58710016-C-A

Variant summary

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

The NM_201648.3(GLYAT):​c.641G>T​(p.Gly214Val) variant causes a missense change. 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: 32)
• Consequence: GLYAT NM_201648.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.78

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

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, 0.972

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLYAT	NM_201648.3	c.641G>T	p.Gly214Val	missense_variant	6/6	ENST00000344743.8	NP_964011.2
GLYAT	XM_017017087.1	c.449G>T	p.Gly150Val	missense_variant	6/6		XP_016872576.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLYAT	ENST00000344743.8	c.641G>T	p.Gly214Val	missense_variant	6/6	1	NM_201648.3	ENSP00000340200.3
GLYAT	ENST00000529732.5	c.641G>T	p.Gly214Val	missense_variant	6/6	5		ENSP00000431688.1
GLYAT	ENST00000611865.4	c.641G>T	p.Gly214Val	missense_variant	5/5	3		ENSP00000484592.1
GLYAT	ENST00000586098.1	c.88+2744G>T		intron_variant		3		ENSP00000468512.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

May 16, 2023

The c.641G>T (p.G214V) alteration is located in exon 6 (coding exon 5) of the GLYAT gene. This alteration results from a G to T substitution at nucleotide position 641, causing the glycine (G) at amino acid position 214 to be replaced by a valine (V). 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	0.59
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.65	D;D;D
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.92	D;.;.
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.97	D;D;D
MetaSVM	Benign	-0.46	T
MutationAssessor	Pathogenic	3.5	H;H;H
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-7.8	.;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0010	.;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.57
MutPred		0.85		Loss of sheet (P = 0.1398);Loss of sheet (P = 0.1398);Loss of sheet (P = 0.1398);
MVP		0.57
MPC		0.14
ClinPred		0.93	D
GERP RS		5.2
Varity_R		0.58
gMVP		0.80

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: chr11-58477489;