7-140028638-G-C

Position:

• chr7-140028638-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022750.4(PARP12):​c.1472C>G​(p.Ser491Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign 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: 3.62

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.229904).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP12	NM_022750.4	c.1472C>G	p.Ser491Cys	missense_variant	9/12	ENST00000263549.8	NP_073587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP12	ENST00000263549.8	c.1472C>G	p.Ser491Cys	missense_variant	9/12	1	NM_022750.4	ENSP00000263549.3

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

Oct 22, 2024

The c.1472C>G (p.S491C) alteration is located in exon 9 (coding exon 9) of the PARP12 gene. This alteration results from a C to G substitution at nucleotide position 1472, causing the serine (S) at amino acid position 491 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	Benign	0.10
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.048
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.059	T;D
Polyphen		0.44	B;.
Vest4		0.38
MutPred		0.40		Loss of disorder (P = 0.0047);.;
MVP		0.57
MPC		0.64
ClinPred		0.95	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.32

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: chr7-139728438;