8-37762701-GTGCGCAT-G

Position:

• chr8-37762701-GTGCGCAT-G

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_007198.4(PLPBP):​c.47_53del​(p.Ala16GlyfsTer3) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLPBP NM_007198.4 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 5.78

Genes affected

PLPBP (HGNC:9457): (pyridoxal phosphate binding protein) This gene encodes a pyridoxal 5'-phosphate binding protein involved in the homeostatic regulation of intracellular pyridoxal 5'-phosphate. This gene has a tumor suppressive effect on hepatocellular carcinoma and other solid tumors of epithelial origin. Naturally occurring mutations in this gene are associated with a pyridoxine-dependent epilepsy. [provided by RefSeq, Mar 2017]

LOC124901934 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 6 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 8-37762701-GTGCGCAT-G is Pathogenic according to our data. Variant chr8-37762701-GTGCGCAT-G is described in ClinVar as [Pathogenic]. Clinvar id is 2066635.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLPBP	NM_007198.4	c.47_53del	p.Ala16GlyfsTer3	frameshift_variant	1/8	ENST00000328195.8	NP_009129.1
LOC124901934	XR_007060889.1	n.444_450del		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLPBP	ENST00000328195.8	c.47_53del	p.Ala16GlyfsTer3	frameshift_variant	1/8	1	NM_007198.4	ENSP00000333551	P1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2021

This sequence change creates a premature translational stop signal (p.Ala16Glyfs*3) in the PROSC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PROSC are known to be pathogenic (PMID: 27912044). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with PROSC-related conditions. This variant is not present in population databases (gnomAD no frequency). -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-37620219;