Variant 4-177335759-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018248.3(NEIL3):c.350C>G(p.Pro117Arg) variant causes a missense change. The variant allele was found at a frequency of 0.108 in 1,593,222 control chromosomes in the GnomAD database, including 10,147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.096 ( 816 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9331 hom. )

Consequence

NEIL3
NM_018248.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.26

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021573305).

BP6

Variant 4-177335759-C-G is Benign according to our data. Variant chr4-177335759-C-G is described in ClinVar as [Benign]. Clinvar id is 2688466.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEIL3	NM_018248.3 link	c.350C>G	p.Pro117Arg	missense_variant	3/10	ENST00000264596.4	NP_060718.3	Q8TAT5
NEIL3	XM_047415894.1 link	c.350C>G	p.Pro117Arg	missense_variant	3/12		XP_047271850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NEIL3	ENST00000264596.4 link	c.350C>G	p.Pro117Arg	missense_variant	3/10	1	NM_018248.3	ENSP00000264596.3	Q8TAT5
NEIL3	ENST00000513321.1 link	n.*36C>G		non_coding_transcript_exon_variant	2/4	1		ENSP00000424735.1	D6RAV1
NEIL3	ENST00000513321.1 link	n.*36C>G		3_prime_UTR_variant	2/4	1		ENSP00000424735.1	D6RAV1

Frequencies

GnomAD3 genomes

AF:

0.0959

AC:

14584

AN:

152032

Hom.:

815

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0582

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.175

Gnomad EAS

AF:

0.0258

Gnomad SAS

AF:

0.0900

Gnomad FIN

AF:

0.0577

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.130

GnomAD3 exomes

AF:

0.106

AC:

25011

AN:

235846

Hom.:

1518

AF XY:

0.107

AC XY:

13624

AN XY:

127450

show subpopulations

Gnomad AFR exome

AF:

0.0597

Gnomad AMR exome

AF:

0.140

Gnomad ASJ exome

AF:

0.178

Gnomad EAS exome

AF:

0.0200

Gnomad SAS exome

AF:

0.0981

Gnomad FIN exome

AF:

0.0650

Gnomad NFE exome

AF:

0.120

Gnomad OTH exome

AF:

0.129

GnomAD4 exome

AF:

0.110

AC:

158254

AN:

1441072

Hom.:

9331

Cov.:

AF XY:

0.111

AC XY:

79245

AN XY:

715770

show subpopulations

Gnomad4 AFR exome

AF:

0.0611

Gnomad4 AMR exome

AF:

0.139

Gnomad4 ASJ exome

AF:

0.179

Gnomad4 EAS exome

AF:

0.0241

Gnomad4 SAS exome

AF:

0.0960

Gnomad4 FIN exome

AF:

0.0644

Gnomad4 NFE exome

AF:

0.114

Gnomad4 OTH exome

AF:

0.115

GnomAD4 genome

AF:

0.0959

AC:

14589

AN:

152150

Hom.:

816

Cov.:

AF XY:

0.0948

AC XY:

7053

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0581

Gnomad4 AMR

AF:

0.133

Gnomad4 ASJ

AF:

0.175

Gnomad4 EAS

AF:

0.0261

Gnomad4 SAS

AF:

0.0903

Gnomad4 FIN

AF:

0.0577

Gnomad4 NFE

AF:

0.116

Gnomad4 OTH

AF:

0.129

Alfa

AF:

0.108

Hom.:

806

Bravo

AF:

0.0986

TwinsUK

AF:

0.119

AC:

440

ALSPAC

AF:

0.109

AC:

422

ESP6500AA

AF:

0.0609

AC:

268

ESP6500EA

AF:

0.118

AC:

1013

ExAC

AF:

0.103

AC:

12449

Asia WGS

AF:

0.0660

AC:

229

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 28% of patients studied by a panel of primary immunodeficiencies. Number of patients: 25. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.55

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.79

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-5.6

REVEL

Benign

0.13

Sift

Uncertain

0.016

Sift4G

Benign

0.074

Polyphen

0.83

Vest4

0.28

MPC

0.26

ClinPred

0.063

GERP RS

5.1

Varity_R

0.38

gMVP

0.68

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