dbSNP rs1372957638: GLYR1:p.Ala199Ser (chr16-4823850-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032569.4(GLYR1):c.595G>T(p.Ala199Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. A199T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GLYR1
NM_032569.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.861

Publications

0 publications found

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]

GLYR1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03297785).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLYR1	NM_032569.4	MANE Select	c.595G>T	p.Ala199Ser	missense	Exon 6 of 16	NP_115958.2
GLYR1	NM_001308096.2		c.595G>T	p.Ala199Ser	missense	Exon 6 of 16	NP_001295025.1	Q49A26-3
GLYR1	NM_001324098.2		c.595G>T	p.Ala199Ser	missense	Exon 6 of 15	NP_001311027.2	Q49A26-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLYR1	ENST00000321919.14	TSL:1 MANE Select	c.595G>T	p.Ala199Ser	missense	Exon 6 of 16	ENSP00000322716.6	Q49A26-1
GLYR1	ENST00000591451.5	TSL:1	c.595G>T	p.Ala199Ser	missense	Exon 6 of 16	ENSP00000468328.1	Q49A26-3
GLYR1	ENST00000589389.5	TSL:1	c.556G>T	p.Ala186Ser	missense	Exon 5 of 14	ENSP00000466570.1	K7EMM8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251476

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111994

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.41

CADD

Benign

2.9

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.026

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.80

M_CAP

Benign

0.017

MetaRNN

Benign

0.033

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

0.86

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.10

REVEL

Benign

0.040

Sift

Benign

0.51

Sift4G

Benign

0.79

Polyphen

0.024

Vest4

0.34

MutPred

0.21

Loss of helix (P = 0.0093)

MVP

0.20

MPC

0.020

ClinPred

0.048

GERP RS

0.012

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.025

gMVP

0.22

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over