7-140037732-T-C

Position:

• chr7-140037732-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_022750.4(PARP12):​c.1307A>G​(p.Tyr436Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PARP12 NM_022750.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.17

Genes affected

PARP12 (HGNC:21919): (poly(ADP-ribose) polymerase family member 12) Enables protein ADP-ribosylase activity. Involved in protein auto-ADP-ribosylation and protein mono-ADP-ribosylation. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.944

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP12	NM_022750.4	c.1307A>G	p.Tyr436Cys	missense_variant	7/12	ENST00000263549.8	NP_073587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP12	ENST00000263549.8	c.1307A>G	p.Tyr436Cys	missense_variant	7/12	1	NM_022750.4	ENSP00000263549.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Dec 10, 2024

The c.1307A>G (p.Y436C) alteration is located in exon 7 (coding exon 7) of the PARP12 gene. This alteration results from a A to G substitution at nucleotide position 1307, causing the tyrosine (Y) at amino acid position 436 to be replaced by a cysteine (C). 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	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Pathogenic	3.6	H
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-8.8	D
REVEL	Uncertain	0.58
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.73		Loss of helix (P = 0.0237);
MVP		0.85
MPC		0.92
ClinPred		1.0	D
GERP RS		4.5
Varity_R		0.91
gMVP		0.91

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: chr7-139737532;