12-102164593-A-C

Position:

• chr12-102164593-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017915.5(PARPBP):​c.651A>C​(p.Gln217His) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q217E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PARPBP NM_017915.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.183

Genes affected

PARPBP (HGNC:26074): (PARP1 binding protein) Predicted to enable DNA binding activity. Involved in negative regulation of double-strand break repair via homologous recombination. Located in chromatin and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06736657).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARPBP	NM_017915.5	c.651A>C	p.Gln217His	missense_variant	5/11	ENST00000327680.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARPBP	ENST00000327680.7	c.651A>C	p.Gln217His	missense_variant	5/11	2	NM_017915.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 29, 2024

The c.651A>C (p.Q217H) alteration is located in exon 5 (coding exon 4) of the PARPBP gene. This alteration results from a A to C substitution at nucleotide position 651, causing the glutamine (Q) at amino acid position 217 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.034	T;T;T;.;T;.
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.71	T;T;T;T;T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.067	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	.;.;L;.;.;.
MutationTaster	Benign	0.98	N;N;N;N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.5	N;N;.;N;N;N
REVEL	Benign	0.014
Sift	Benign	0.17	T;T;.;T;T;T
Sift4G	Benign	0.29	T;T;T;T;T;T
Polyphen		0.010	B;B;B;B;.;.
Vest4		0.12
MutPred		0.36		Loss of solvent accessibility (P = 0.0635);.;.;.;.;.;
MVP		0.32
ClinPred		0.066	T
GERP RS		-2.1
Varity_R		0.040
gMVP		0.45

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-102558371;