chr8-37762692-G-C

Variant names:

• chr8-37762692-G-C
• rs746074808
• NM_007198.4:c.33G>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_007198.4(PLPBP):​c.33G>C​(p.Leu11Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L11L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLPBP NM_007198.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 0 publications found

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]

PLPBP Gene-Disease associations (from GenCC):

• epilepsy, early-onset, vitamin B6-dependent

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• pyridoxine-dependent epilepsy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000304882 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP7: Synonymous conserved (PhyloP=1.3 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007198.4. 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
	PLPBP	NM_007198.4	MANE Select	c.33G>C	p.Leu11Leu	synonymous	Exon 1 of 8	NP_009129.1	O94903
	PLPBP	NM_001349346.2		c.33G>C	p.Leu11Leu	synonymous	Exon 1 of 8	NP_001336275.1
	PLPBP	NM_001349347.2		c.33G>C	p.Leu11Leu	synonymous	Exon 1 of 8	NP_001336276.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLPBP	ENST00000328195.8	TSL:1 MANE Select	c.33G>C	p.Leu11Leu	synonymous	Exon 1 of 8	ENSP00000333551.3	O94903
	PLPBP	ENST00000872272.1		c.33G>C	p.Leu11Leu	synonymous	Exon 1 of 8	ENSP00000542331.1
	PLPBP	ENST00000958638.1		c.33G>C	p.Leu11Leu	synonymous	Exon 1 of 8	ENSP00000628697.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	6.6
DANN	Benign	0.73
PhyloP100		1.3
PromoterAI		0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs746074808; hg19: chr8-37620210;