chr9-37422766-C-T

Position:

chr9-37422766-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000318158.11(GRHPR):c.16C>T(p.Leu6Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 1,593,940 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 36 hom. )

Consequence

GRHPR
ENST00000318158.11 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.28

Variant links:

Genes affected

GRHPR (HGNC:4570): (glyoxylate and hydroxypyruvate reductase) This gene encodes an enzyme with hydroxypyruvate reductase, glyoxylate reductase, and D-glycerate dehydrogenase enzymatic activities. The enzyme has widespread tissue expression and has a role in metabolism. Type II hyperoxaluria is caused by mutations in this gene. [provided by RefSeq, Jul 2008]

GRHPR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0075918436).

BP6

Variant 9-37422766-C-T is Benign according to our data. Variant chr9-37422766-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 366851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0013 (198/152322) while in subpopulation SAS AF= 0.0139 (67/4824). AF 95% confidence interval is 0.0112. There are 2 homozygotes in gnomad4. There are 121 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRHPR	NM_012203.2 linkuse as main transcript	c.16C>T	p.Leu6Phe	missense_variant	1/9	ENST00000318158.11	NP_036335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRHPR	ENST00000318158.11 linkuse as main transcript	c.16C>T	p.Leu6Phe	missense_variant	1/9	1	NM_012203.2	ENSP00000313432	P1	Q9UBQ7-1

Frequencies

GnomAD3 genomes

AF:

0.00129

AC:

197

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00750

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0139

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00115

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00321

AC:

703

AN:

218716

Hom.:

AF XY:

0.00401

AC XY:

477

AN XY:

118934

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00121

Gnomad ASJ exome

AF:

0.00540

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0174

Gnomad FIN exome

AF:

0.0000542

Gnomad NFE exome

AF:

0.00120

Gnomad OTH exome

AF:

0.00332

GnomAD4 exome

AF:

0.00222

AC:

3204

AN:

1441618

Hom.:

Cov.:

AF XY:

0.00274

AC XY:

1964

AN XY:

715688

show subpopulations

Gnomad4 AFR exome

AF:

0.000182

Gnomad4 AMR exome

AF:

0.00115

Gnomad4 ASJ exome

AF:

0.00620

Gnomad4 EAS exome

AF:

0.0000521

Gnomad4 SAS exome

AF:

0.0178

Gnomad4 FIN exome

AF:

0.0000590

Gnomad4 NFE exome

AF:

0.00113

Gnomad4 OTH exome

AF:

0.00316

GnomAD4 genome

AF:

0.00130

AC:

198

AN:

152322

Hom.:

Cov.:

AF XY:

0.00162

AC XY:

121

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00750

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0139

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00116

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00138

Hom.:

Bravo

AF:

0.00116

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00175

AC:

ExAC

AF:

0.00309

AC:

372

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary hyperoxaluria, type II

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	May 18, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Oct 28, 2019	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 17, 2020	- -

GRHPR-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 31, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.041

T;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.74

T;T

MetaRNN

Benign

0.0076

T;T

MetaSVM

Uncertain

0.21

MutationAssessor

Uncertain

2.9

M;.

MutationTaster

Benign

0.81

D;D

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.5

N;.

REVEL

Uncertain

0.30

Sift

Benign

0.036

D;.

Sift4G

Benign

0.066

T;T

Polyphen

0.29

B;.

Vest4

0.26

MVP

0.85

MPC

0.62

ClinPred

0.097

GERP RS

4.0

Varity_R

0.27

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over