Genetic Variant NEIL3:p.Arg15Arg (chr4-177309998-C-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_018248.3(NEIL3):c.45C>A(p.Arg15Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,609,634 control chromosomes in the GnomAD database, including 38,459 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.20 ( 3021 hom., cov: 33)

Exomes 𝑓: 0.22 ( 35438 hom. )

Consequence

NEIL3
NM_018248.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.224

Variant links:

Genes affected

NEIL3 (HGNC:24573): (nei like DNA glycosylase 3) NEIL3 belongs to a class of DNA glycosylases homologous to the bacterial Fpg/Nei family. These glycosylases initiate the first step in base excision repair by cleaving bases damaged by reactive oxygen species and introducing a DNA strand break via the associated lyase reaction (Bandaru et al., 2002 [PubMed 12509226]).[supplied by OMIM, Mar 2008]

NEIL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 4-177309998-C-A is Benign according to our data. Variant chr4-177309998-C-A is described in ClinVar as [Benign]. Clinvar id is 2688445.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.224 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL3	NM_018248.3 link	c.45C>A	p.Arg15Arg	synonymous_variant	Exon 1 of 10	ENST00000264596.4	NP_060718.3	Q8TAT5
NEIL3	XM_047415894.1 link	c.45C>A	p.Arg15Arg	synonymous_variant	Exon 1 of 12		XP_047271850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEIL3	ENST00000264596.4 link	c.45C>A	p.Arg15Arg	synonymous_variant	Exon 1 of 10	1	NM_018248.3	ENSP00000264596.3		Q8TAT5
NEIL3	ENST00000513321.1 link	n.45C>A		non_coding_transcript_exon_variant	Exon 1 of 4	1		ENSP00000424735.1		D6RAV1

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29781

AN:

152044

Hom.:

3017

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.186

Gnomad AMR

AF:

0.199

Gnomad ASJ

AF:

0.229

Gnomad EAS

AF:

0.142

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.208

GnomAD3 exomes

AF:

0.201

AC:

49607

AN:

246254

Hom.:

5192

AF XY:

0.205

AC XY:

27438

AN XY:

133716

show subpopulations

Gnomad AFR exome

AF:

0.146

Gnomad AMR exome

AF:

0.178

Gnomad ASJ exome

AF:

0.229

Gnomad EAS exome

AF:

0.131

Gnomad SAS exome

AF:

0.207

Gnomad FIN exome

AF:

0.190

Gnomad NFE exome

AF:

0.225

Gnomad OTH exome

AF:

0.225

GnomAD4 exome

AF:

0.219

AC:

318548

AN:

1457472

Hom.:

35438

Cov.:

AF XY:

0.219

AC XY:

158798

AN XY:

724990

show subpopulations

Gnomad4 AFR exome

AF:

0.151

Gnomad4 AMR exome

AF:

0.181

Gnomad4 ASJ exome

AF:

0.235

Gnomad4 EAS exome

AF:

0.155

Gnomad4 SAS exome

AF:

0.202

Gnomad4 FIN exome

AF:

0.191

Gnomad4 NFE exome

AF:

0.227

Gnomad4 OTH exome

AF:

0.215

GnomAD4 genome

AF:

0.196

AC:

29809

AN:

152162

Hom.:

3021

Cov.:

AF XY:

0.195

AC XY:

14482

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.151

Gnomad4 AMR

AF:

0.199

Gnomad4 ASJ

AF:

0.229

Gnomad4 EAS

AF:

0.142

Gnomad4 SAS

AF:

0.202

Gnomad4 FIN

AF:

0.189

Gnomad4 NFE

AF:

0.225

Gnomad4 OTH

AF:

0.206

Alfa

AF:

0.213

Hom.:

4729

Bravo

AF:

0.192

Asia WGS

AF:

0.177

AC:

617

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 38% of patients studied by a panel of primary immunodeficiencies. Number of patients: 33. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.92

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over