rs1783942283

Variant names:

• chr7-4860096-G-A
• rs1783942283
• NM_020144.5:c.1715C>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_020144.5(PAPOLB):​c.1715C>T​(p.Ala572Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: PAPOLB NM_020144.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.16

Genes affected

PAPOLB (HGNC:15970): (poly(A) polymerase beta) Predicted to enable polynucleotide adenylyltransferase activity. Predicted to be involved in mRNA polyadenylation. Predicted to be located in endoplasmic reticulum. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RADIL (HGNC:22226): (Rap associating with DIL domain) Predicted to enable GTPase binding activity. Acts upstream of or within substrate adhesion-dependent cell spreading. Located in microtubule. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048169285).
• BP6: Variant 7-4860096-G-A is Benign according to our data. Variant chr7-4860096-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2250320.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPOLB	NM_020144.5	c.1715C>T	p.Ala572Val	missense_variant	Exon 1 of 1	ENST00000404991.2	NP_064529.4
RADIL	NM_018059.5	c.535+17509C>T		intron_variant	Intron 2 of 14	ENST00000399583.4	NP_060529.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAPOLB	ENST00000404991.2	c.1715C>T	p.Ala572Val	missense_variant	Exon 1 of 1	6	NM_020144.5	ENSP00000384700.2
RADIL	ENST00000399583.4	c.535+17509C>T		intron_variant	Intron 2 of 14	5	NM_018059.5	ENSP00000382492.3
RADIL	ENST00000445392.5	n.535+17509C>T		intron_variant	Intron 2 of 14	5		ENSP00000413403.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461686 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727122

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Sep 16, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	10
DANN	Benign	0.91
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.26	T
REVEL	Benign	0.040
Sift4G	Benign	0.26	T
Polyphen		0.0010	B
Vest4		0.032
MVP		0.26
MPC		0.10
ClinPred		0.043	T
GERP RS		1.3
gMVP		0.10

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

LitVar

Other links and lift over

dbSNP: rs1783942283; hg19: chr7-4899727; COSMIC: COSV68200340;