16-4814619-C-A

Variant names:

• chr16-4814619-C-A
• rs752741681
• NM_032569.4:c.935G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032569.4(GLYR1):​c.935G>T​(p.Arg312Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R312H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GLYR1 NM_032569.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.82
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.935G>T	p.Arg312Leu	missense	Exon 11 of 16	NP_115958.2
	GLYR1	NM_001308096.2		c.917G>T	p.Arg306Leu	missense	Exon 11 of 16	NP_001295025.1	Q49A26-3
	GLYR1	NM_001324098.2		c.884G>T	p.Arg295Leu	missense	Exon 10 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.935G>T	p.Arg312Leu	missense	Exon 11 of 16	ENSP00000322716.6	Q49A26-1
	GLYR1	ENST00000591451.5	TSL:1	c.917G>T	p.Arg306Leu	missense	Exon 11 of 16	ENSP00000468328.1	Q49A26-3
	GLYR1	ENST00000589389.5	TSL:1	c.845G>T	p.Arg282Leu	missense	Exon 9 of 14	ENSP00000466570.1	K7EMM8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.0034	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.81	L
PhyloP100		5.8
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.12
Sift	Benign	0.10	T
Sift4G	Benign	0.13	T
Polyphen		0.0030	B
Vest4		0.76
MutPred		0.46		Loss of solvent accessibility (P = 0.0606)
MVP		0.10
MPC		0.82
ClinPred		0.95	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.55
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs752741681; hg19: chr16-4864620;