11-58710008-C-G

Position:

• chr11-58710008-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_201648.3(GLYAT):​c.649G>C​(p.Val217Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000644 in 1,614,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: GLYAT NM_201648.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.07

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15186319).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLYAT	NM_201648.3	c.649G>C	p.Val217Leu	missense_variant	6/6	ENST00000344743.8	NP_964011.2
GLYAT	XM_017017087.1	c.457G>C	p.Val153Leu	missense_variant	6/6		XP_016872576.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLYAT	ENST00000344743.8	c.649G>C	p.Val217Leu	missense_variant	6/6	1	NM_201648.3	ENSP00000340200.3
GLYAT	ENST00000529732.5	c.649G>C	p.Val217Leu	missense_variant	6/6	5		ENSP00000431688.1
GLYAT	ENST00000611865.4	c.649G>C	p.Val217Leu	missense_variant	5/5	3		ENSP00000484592.1
GLYAT	ENST00000586098.1	c.88+2752G>C		intron_variant		3		ENSP00000468512.1

Frequencies

GnomAD3 genomes AF: 0.000309 AC: 47 AN: 152230 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000941

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.0000996 AC: 25 AN: 251074 Hom.: 0 AF XY: 0.0000958 AC XY: 13 AN XY: 135698

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000529

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000390 AC: 57 AN: 1461782 Hom.: 0 Cov.: 32 AF XY: 0.0000316 AC XY: 23 AN XY: 727186

Gnomad4 AFR exome AF: 0.000448

Gnomad4 AMR exome AF: 0.000157

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000207

Gnomad4 OTH exome AF: 0.0000994

GnomAD4 genome AF: 0.000309 AC: 47 AN: 152348 Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23 AN XY: 74494

Gnomad4 AFR AF: 0.000938

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.0000847 Hom.: 0

Bravo AF: 0.000314

ESP6500AA AF: 0.000909 AC: 4

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000148 AC: 18

EpiCase AF: 0.00

EpiControl AF: 0.000119

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

Oct 21, 2021

The c.649G>C (p.V217L) alteration is located in exon 6 (coding exon 5) of the GLYAT gene. This alteration results from a G to C substitution at nucleotide position 649, causing the valine (V) at amino acid position 217 to be replaced by a leucine (L). 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	Uncertain	0.42
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;T;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.80	T;.;.
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Pathogenic	3.3	M;M;M
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.5	.;N;N
REVEL	Uncertain	0.31
Sift	Uncertain	0.0050	.;D;D
Sift4G	Uncertain	0.0090	D;D;D
Polyphen		0.97	D;D;D
Vest4		0.42
MutPred		0.60		Gain of catalytic residue at V217 (P = 0.0609);Gain of catalytic residue at V217 (P = 0.0609);Gain of catalytic residue at V217 (P = 0.0609);
MVP		0.41
MPC		0.11
ClinPred		0.18	T
GERP RS		5.2
Varity_R		0.25
gMVP		0.63

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: rs147885245; hg19: chr11-58477481;