Genetic Variant NM_018248.3:c.50G>T (chr4-177310003-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018248.3(NEIL3):c.50G>T(p.Arg17Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R17Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NEIL3
NM_018248.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.207

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.091340184).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018248.3. 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
	NEIL3	NM_018248.3	MANE Select	c.50G>T	p.Arg17Leu	missense	Exon 1 of 10	NP_060718.3	Q8TAT5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEIL3	ENST00000264596.4	TSL:1 MANE Select	c.50G>T	p.Arg17Leu	missense	Exon 1 of 10	ENSP00000264596.3	Q8TAT5
NEIL3	ENST00000513321.1	TSL:1	n.50G>T		non_coding_transcript_exon	Exon 1 of 4	ENSP00000424735.1	D6RAV1
NEIL3	ENST00000905043.1		c.50G>T	p.Arg17Leu	missense	Exon 1 of 10	ENSP00000575102.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000810

AC:

AN:

246908

AF XY:

0.0000149

show subpopulations

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:

0.00

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458470

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725552

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33302

American (AMR)

AF:

0.00

AC:

AN:

44522

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26038

East Asian (EAS)

AF:

0.00

AC:

AN:

39502

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85926

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53320

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4694

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110966

Other (OTH)

AF:

0.0000166

AC:

AN:

60200

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.036

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.78

M_CAP

Benign

0.0070

MetaRNN

Benign

0.091

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

0.21

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.9

REVEL

Benign

0.095

Sift

Benign

0.051

Sift4G

Uncertain

0.016

Polyphen

0.28

Vest4

0.22

MutPred

0.47

Loss of MoRF binding (P = 0.0124)

MVP

0.41

MPC

0.19

ClinPred

0.64

GERP RS

0.30

PromoterAI

-0.025

Neutral

(source)

Varity_R

0.089

gMVP

0.61

Mutation Taster

=87/13

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over