9-37436635-CCTCTCTCTCTCT-CCT

Variant names:

• chr9-37436635-CCTCTCTCTCT-C
• rs34302950
• NM_012203.2:c.866-18_866-9delTCTCTCTCTC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_012203.2(GRHPR):​c.866-18_866-9delTCTCTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000218 in 1,374,128 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: GRHPR NM_012203.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.668
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• primary hyperoxaluria type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Myriad Women’s Health, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 9-37436635-CCTCTCTCTCT-C is Benign according to our data. Variant chr9-37436635-CCTCTCTCTCT-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2899870.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012203.2. 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
	GRHPR	NM_012203.2	MANE Select	c.866-18_866-9delTCTCTCTCTC		intron	N/A	NP_036335.1	A0A384N605

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRHPR	ENST00000318158.11	TSL:1 MANE Select	c.866-18_866-9delTCTCTCTCTC		intron	N/A	ENSP00000313432.6	Q9UBQ7-1
	GRHPR	ENST00000460882.5	TSL:1	n.893-18_893-9delTCTCTCTCTC		intron	N/A
	GRHPR	ENST00000874646.1		c.974-18_974-9delTCTCTCTCTC		intron	N/A	ENSP00000544705.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000218 AC: 3 AN: 1374128 Hom.: 0 AF XY: 0.00000292 AC XY: 2 AN XY: 684104

African (AFR) AF: 0.00 AC: 0 AN: 31460

American (AMR) AF: 0.00 AC: 0 AN: 41988

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24672

East Asian (EAS) AF: 0.00 AC: 0 AN: 36556

South Asian (SAS) AF: 0.00 AC: 0 AN: 81088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5512

European-Non Finnish (NFE) AF: 0.00000287 AC: 3 AN: 1045864

Other (OTH) AF: 0.00 AC: 0 AN: 56730

GnomAD4 genome Cov.: 28

Alfa AF: 0.00 Hom.: 82

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.67

Splicing

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

Other links and lift over

dbSNP: rs34302950; hg19: chr9-37436632;