rs982521520

Variant names:

• chr8-37762667-G-A
• rs982521520
• NM_007198.4:c.8G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-37762667-G-A
• chr8-37762667-G-C
• chr8-37762667-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007198.4(PLPBP):​c.8G>A​(p.Arg3Lys) variant causes a missense 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R3R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLPBP NM_007198.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.43
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11958873).

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.8G>A	p.Arg3Lys	missense	Exon 1 of 8	NP_009129.1	O94903
	PLPBP	NM_001349346.2		c.8G>A	p.Arg3Lys	missense	Exon 1 of 8	NP_001336275.1
	PLPBP	NM_001349347.2		c.8G>A	p.Arg3Lys	missense	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.8G>A	p.Arg3Lys	missense	Exon 1 of 8	ENSP00000333551.3	O94903
	PLPBP	ENST00000872272.1		c.8G>A	p.Arg3Lys	missense	Exon 1 of 8	ENSP00000542331.1
	PLPBP	ENST00000958638.1		c.8G>A	p.Arg3Lys	missense	Exon 1 of 8	ENSP00000628697.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000285 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.089	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.4
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.050
Sift	Benign	0.57	T
Sift4G	Benign	0.79	T
Polyphen		0.0	B
Vest4		0.21
MutPred		0.28		Gain of ubiquitination at R3 (P = 0.017)
MVP		0.38
MPC		0.39
ClinPred		0.69	D
GERP RS		3.3
PromoterAI		0.0062	Neutral
Varity_R		0.18
gMVP		0.65
Mutation Taster		=73/27	polymorphism

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: rs982521520; hg19: chr8-37620185;