11-58710104-A-G

Position:

• chr11-58710104-A-G

Variant summary

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

The NM_201648.3(GLYAT):​c.553T>C​(p.Trp185Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000301 in 1,461,762 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: GLYAT NM_201648.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.30

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, 0.987

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLYAT	NM_201648.3	c.553T>C	p.Trp185Arg	missense_variant	6/6	ENST00000344743.8	NP_964011.2
GLYAT	XM_017017087.1	c.361T>C	p.Trp121Arg	missense_variant	6/6		XP_016872576.1
GLYAT	NM_005838.4	c.*482T>C		3_prime_UTR_variant	5/5		NP_005829.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLYAT	ENST00000344743.8	c.553T>C	p.Trp185Arg	missense_variant	6/6	1	NM_201648.3	ENSP00000340200.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000301 AC: 44 AN: 1461762 Hom.: 0 Cov.: 32 AF XY: 0.0000330 AC XY: 24 AN XY: 727174

Gnomad4 AFR exome AF: 0.0000299

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: 0.0000369

Gnomad4 OTH exome AF: 0.0000331

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

Jul 14, 2021

The c.553T>C (p.W185R) alteration is located in exon 6 (coding exon 5) of the GLYAT gene. This alteration results from a T to C substitution at nucleotide position 553, causing the tryptophan (W) at amino acid position 185 to be replaced by an arginine (R). 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	0.97
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T;T;T
Eigen	Pathogenic	0.76
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T;.;.
M_CAP	Benign	0.072	D
MetaRNN	Pathogenic	0.99	D;D;D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Pathogenic	4.0	H;H;H
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-13	.;D;D
REVEL	Uncertain	0.58
Sift	Pathogenic	0.0	.;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.86
MutPred		0.95		Gain of disorder (P = 0.0141);Gain of disorder (P = 0.0141);Gain of disorder (P = 0.0141);
MVP		0.48
MPC		0.15
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.90
gMVP		0.87

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: chr11-58477577;