rs61741951

Variant names:

• chr13-24434735-G-C
• rs61741951
• NM_006437.4:c.4406C>G

Your query was ambiguous. Multiple possible variants found:

• chr13-24434735-G-C
• chr13-24434735-G-A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_006437.4(PARP4):​c.4406C>G​(p.Ala1469Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00541 in 1,613,896 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0056 (39 hom.)
• Consequence: PARP4 NM_006437.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.82
• Publications: 3 publications found

Genes affected

PARP4 (HGNC:271): (poly(ADP-ribose) polymerase family member 4) This gene encodes poly(ADP-ribosyl)transferase-like 1 protein, which is capable of catalyzing a poly(ADP-ribosyl)ation reaction. This protein has a catalytic domain which is homologous to that of poly (ADP-ribosyl) transferase, but lacks an N-terminal DNA binding domain which activates the C-terminal catalytic domain of poly (ADP-ribosyl) transferase. Since this protein is not capable of binding DNA directly, its transferase activity may be activated by other factors such as protein-protein interaction mediated by the extensive carboxyl terminus. [provided by RefSeq, Jul 2008]

TPTE2P6 (HGNC:42644): (TPTE2 pseudogene 6)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0070907474).
• BP6: Variant 13-24434735-G-C is Benign according to our data. Variant chr13-24434735-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2643685.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006437.4. 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
	PARP4	NM_006437.4	MANE Select	c.4406C>G	p.Ala1469Gly	missense	Exon 31 of 34	NP_006428.2	Q9UKK3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP4	ENST00000381989.4	TSL:1 MANE Select	c.4406C>G	p.Ala1469Gly	missense	Exon 31 of 34	ENSP00000371419.3	Q9UKK3
	PARP4	ENST00000908086.1		c.4406C>G	p.Ala1469Gly	missense	Exon 32 of 35	ENSP00000578145.1
	PARP4	ENST00000934618.1		c.4406C>G	p.Ala1469Gly	missense	Exon 32 of 35	ENSP00000604677.1

Frequencies

GnomAD3 genomes AF: 0.00352 AC: 535 AN: 152168 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.00380

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00235

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00559

Gnomad OTH AF: 0.00479

GnomAD2 exomes AF: 0.00315 AC: 787 AN: 249842 AF XY: 0.00311

Gnomad AFR exome AF: 0.00102

Gnomad AMR exome AF: 0.00290

Gnomad ASJ exome AF: 0.000498

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00245

Gnomad NFE exome AF: 0.00524

Gnomad OTH exome AF: 0.00313

GnomAD4 exome AF: 0.00560 AC: 8191 AN: 1461610 Hom.: 39 Cov.: 38 AF XY: 0.00545 AC XY: 3961 AN XY: 727096

African (AFR) AF: 0.00105 AC: 35 AN: 33472

American (AMR) AF: 0.00304 AC: 136 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.000650 AC: 17 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86242

European-Finnish (FIN) AF: 0.00271 AC: 145 AN: 53408

Middle Eastern (MID) AF: 0.000352 AC: 2 AN: 5674

European-Non Finnish (NFE) AF: 0.00684 AC: 7606 AN: 1111914

Other (OTH) AF: 0.00404 AC: 244 AN: 60384

GnomAD4 genome AF: 0.00351 AC: 535 AN: 152286 Hom.: 2 Cov.: 33 AF XY: 0.00321 AC XY: 239 AN XY: 74468

African (AFR) AF: 0.00120 AC: 50 AN: 41552

American (AMR) AF: 0.00379 AC: 58 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00235 AC: 25 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00559 AC: 380 AN: 68026

Other (OTH) AF: 0.00474 AC: 10 AN: 2110

Alfa AF: 0.00411 Hom.: 0

Bravo AF: 0.00348

TwinsUK AF: 0.00755 AC: 28

ALSPAC AF: 0.00727 AC: 28

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.00558 AC: 48

ExAC AF: 0.00306 AC: 372

Asia WGS AF: 0.000577 AC: 3 AN: 3478

EpiCase AF: 0.00562

EpiControl AF: 0.00611

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.095
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.76
DANN	Benign	0.70
DEOGEN2	Benign	0.043	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.00052	T
MetaRNN	Benign	0.0071	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.55	N
PhyloP100		-1.8
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.014
Sift	Benign	0.38	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.11
MVP		0.31
MPC		0.13
ClinPred		0.0028	T
GERP RS		-5.6
Varity_R		0.016
gMVP		0.10
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs61741951; hg19: chr13-25008873;