11-58710016-C-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_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

Scores

4
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.78
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank MANE Protein UniProt
GLYATNM_201648.3 linkc.641G>T p.Gly214Val missense_variant Exon 6 of 6 ENST00000344743.8 NP_964011.2 Q6IB77-1A0A384P5E3
GLYATXM_017017087.1 linkc.449G>T p.Gly150Val missense_variant Exon 6 of 6 XP_016872576.1
GLYATNM_005838.4 linkc.*570G>T downstream_gene_variant NP_005829.3 Q6IB77-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GLYATENST00000344743.8 linkc.641G>T p.Gly214Val missense_variant Exon 6 of 6 1 NM_201648.3 ENSP00000340200.3 Q6IB77-1

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
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 16, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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; API