rs1555500532

Variant names:

• chr16-4823861-C-A
• rs1555500532
• NM_032569.4:c.584G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032569.4(GLYR1):​c.584G>T​(p.Gly195Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,878 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G195R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GLYR1 NM_032569.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.17
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29277933).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032569.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLYR1	NM_032569.4	MANE Select	c.584G>T	p.Gly195Val	missense	Exon 6 of 16	NP_115958.2
	GLYR1	NM_001308096.2		c.584G>T	p.Gly195Val	missense	Exon 6 of 16	NP_001295025.1	Q49A26-3
	GLYR1	NM_001324098.2		c.584G>T	p.Gly195Val	missense	Exon 6 of 15	NP_001311027.2	Q49A26-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLYR1	ENST00000321919.14	TSL:1 MANE Select	c.584G>T	p.Gly195Val	missense	Exon 6 of 16	ENSP00000322716.6	Q49A26-1
	GLYR1	ENST00000591451.5	TSL:1	c.584G>T	p.Gly195Val	missense	Exon 6 of 16	ENSP00000468328.1	Q49A26-3
	GLYR1	ENST00000589389.5	TSL:1	c.545G>T	p.Gly182Val	missense	Exon 5 of 14	ENSP00000466570.1	K7EMM8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461878 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727236

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	GLYR1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.054	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	0.81	L
PhyloP100		4.2
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.14
Sift	Benign	0.031	D
Sift4G	Benign	0.21	T
Polyphen		0.081	B
Vest4		0.63
MutPred		0.25		Loss of catalytic residue at A194 (P = 0.1328)
MVP		0.61
MPC		0.15
ClinPred		0.87	D
GERP RS		5.4
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.15
gMVP		0.45
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

dbSNP: rs1555500532; hg19: chr16-4873862;