rs796052867

Variant names:

• chr17-47941669-GCCC-G
• rs796052867
• NM_018129.4:c.-3_-1delCCC

Your query was ambiguous. Multiple possible variants found:

• chr17-47941669-GCCC-G
• chr17-47941669-GCCC-GCC
• chr17-47941669-GCCC-GCCCC

Variant summary

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

The NM_018129.4(PNPO):​c.-3_-1delCCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000728 in 1,373,130 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: PNPO NM_018129.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184
• Publications: 0 publications found

Genes affected

PNPO (HGNC:30260): (pyridoxamine 5'-phosphate oxidase) The enzyme encoded by this gene catalyzes the terminal, rate-limiting step in the synthesis of pyridoxal 5'-phosphate, also known as vitamin B6. Vitamin B6 is a required co-factor for enzymes involved in both homocysteine metabolism and synthesis of neurotransmitters such as catecholamine. Mutations in this gene result in pyridoxamine 5'-phosphate oxidase (PNPO) deficiency, a form of neonatal epileptic encephalopathy. [provided by RefSeq, Oct 2008]

PNPO Gene-Disease associations (from GenCC):

• pyridoxal phosphate-responsive seizures

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), G2P

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_018129.4. 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
	PNPO	NM_018129.4	MANE Select	c.-3_-1delCCC		5_prime_UTR	Exon 1 of 7	NP_060599.1	Q9NVS9-1
	PNPO	NM_001436305.1		c.-3_-1delCCC		5_prime_UTR	Exon 1 of 6	NP_001423234.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPO	ENST00000642017.2	MANE Select	c.-3_-1delCCC		5_prime_UTR	Exon 1 of 7	ENSP00000493302.2	Q9NVS9-1
	PNPO	ENST00000225573.5	TSL:1	c.-3_-1delCCC		5_prime_UTR	Exon 1 of 6	ENSP00000225573.5	Q9NVS9-4
	PNPO	ENST00000958514.1		c.-3_-1delCCC		5_prime_UTR	Exon 1 of 7	ENSP00000628573.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.28e-7 AC: 1 AN: 1373130 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 673086

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31040

American (AMR) AF: 0.00 AC: 0 AN: 34926

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24700

East Asian (EAS) AF: 0.00 AC: 0 AN: 35058

South Asian (SAS) AF: 0.00 AC: 0 AN: 78302

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46856

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 9.42e-7 AC: 1 AN: 1061530

Other (OTH) AF: 0.00 AC: 0 AN: 56582

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.18

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: rs796052867; hg19: chr17-46019035;