NM_006437.4:c.4980-8dupT

Variant names:

• chr13-24421321-T-TA
• rs753943201
• NM_006437.4:c.4980-8dupT

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_006437.4(PARP4):​c.4980-8dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (2116 hom., cov: 0)
  • Exomes 𝑓: 0.10 (115 hom.)
  • Failed GnomAD Quality Control
• Consequence: PARP4 NM_006437.4 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.76
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 13-24421321-T-TA is Benign according to our data. Variant chr13-24421321-T-TA is described in ClinVar as Benign. ClinVar VariationId is 2796426.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2116 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.4980-8dupT		splice_region intron	N/A	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.4980-8_4980-7insT		splice_region intron	N/A	ENSP00000371419.3	Q9UKK3
	PARP4	ENST00000908086.1		c.4980-8_4980-7insT		splice_region intron	N/A	ENSP00000578145.1
	PARP4	ENST00000934618.1		c.4980-8_4980-7insT		splice_region intron	N/A	ENSP00000604677.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 24523 AN: 111128 Hom.: 2119 Cov.: 0

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.295

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.205

GnomAD2 exomes AF: 0.0000713 AC: 1 AN: 14024 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000199

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.101 AC: 95807 AN: 952748 Hom.: 115 Cov.: 15 AF XY: 0.102 AC XY: 47696 AN XY: 468880

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0880 AC: 1954 AN: 22194

American (AMR) AF: 0.132 AC: 2194 AN: 16664

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 2375 AN: 15050

East Asian (EAS) AF: 0.155 AC: 4433 AN: 28558

South Asian (SAS) AF: 0.0653 AC: 3340 AN: 51168

European-Finnish (FIN) AF: 0.154 AC: 5781 AN: 37610

Middle Eastern (MID) AF: 0.139 AC: 370 AN: 2666

European-Non Finnish (NFE) AF: 0.0954 AC: 70415 AN: 738364

Other (OTH) AF: 0.122 AC: 4945 AN: 40474

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.220 AC: 24506 AN: 111192 Hom.: 2116 Cov.: 0 AF XY: 0.209 AC XY: 11140 AN XY: 53198

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.169 AC: 5321 AN: 31434

American (AMR) AF: 0.204 AC: 2236 AN: 10942

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 725 AN: 2636

East Asian (EAS) AF: 0.261 AC: 1029 AN: 3940

South Asian (SAS) AF: 0.154 AC: 532 AN: 3452

European-Finnish (FIN) AF: 0.244 AC: 1529 AN: 6264

Middle Eastern (MID) AF: 0.294 AC: 67 AN: 228

European-Non Finnish (NFE) AF: 0.253 AC: 12650 AN: 50082

Other (OTH) AF: 0.208 AC: 306 AN: 1472

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.133 Hom.: 250

ClinVar

ClinVar submissions

Significance: 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
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs753943201; hg19: chr13-24995459;