16-4832002-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032569.4(GLYR1):​c.514G>A​(p.Gly172Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GLYR1
NM_032569.4 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.43
Variant links:
Genes affected
GLYR1 (HGNC:24434): (glyoxylate reductase 1 homolog) Enables DNA binding activity; methylated histone binding activity; and nucleosome binding activity. Involved in positive regulation of histone acetylation and positive regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm. Part of nucleosome. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

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=0.20146573).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GLYR1NM_032569.4 linkc.514G>A p.Gly172Ser missense_variant Exon 5 of 16 ENST00000321919.14 NP_115958.2 Q49A26-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GLYR1ENST00000321919.14 linkc.514G>A p.Gly172Ser missense_variant Exon 5 of 16 1 NM_032569.4 ENSP00000322716.6 Q49A26-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461532
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727072
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
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
Apr 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.514G>A (p.G172S) alteration is located in exon 5 (coding exon 5) of the GLYR1 gene. This alteration results from a G to A substitution at nucleotide position 514, causing the glycine (G) at amino acid position 172 to be replaced by a serine (S). 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
Benign
0.18
BayesDel_addAF
Benign
0.010
T
BayesDel_noAF
Benign
-0.22
CADD
Uncertain
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.020
T;.;T
Eigen
Benign
0.019
Eigen_PC
Benign
0.22
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.94
D;D;D
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.20
T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
0.81
L;L;.
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-0.10
N;.;.
REVEL
Benign
0.15
Sift
Benign
0.28
T;.;.
Sift4G
Benign
0.17
T;T;D
Polyphen
0.27
B;B;.
Vest4
0.62
MutPred
0.22
Gain of phosphorylation at G172 (P = 2e-04);Gain of phosphorylation at G172 (P = 2e-04);.;
MVP
0.18
MPC
0.028
ClinPred
0.58
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.1
Varity_R
0.12
gMVP
0.24

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: chr16-4882003; API