Genetic Variant NEIL3:p.Ala39Pro (chr4-177310068-G-C) – 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.115G>C(p.Ala39Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. A39V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

NEIL3
NM_018248.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.24

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:

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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=0.16814733).

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.115G>C	p.Ala39Pro	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.115G>C	p.Ala39Pro	missense	Exon 1 of 10	ENSP00000264596.3	Q8TAT5
NEIL3	ENST00000513321.1	TSL:1	n.115G>C		non_coding_transcript_exon	Exon 1 of 4	ENSP00000424735.1	D6RAV1
NEIL3	ENST00000905043.1		c.115G>C	p.Ala39Pro	missense	Exon 1 of 10	ENSP00000575102.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1447168

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

719584

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32562

American (AMR)

AF:

0.00

AC:

AN:

42744

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25710

East Asian (EAS)

AF:

0.00

AC:

AN:

38648

South Asian (SAS)

AF:

0.00

AC:

AN:

84658

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52558

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4492

European-Non Finnish (NFE)

AF:

9.04e-7

AC:

AN:

1106178

Other (OTH)

AF:

0.00

AC:

AN:

59618

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.40

M_CAP

Benign

0.012

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

1.2

PrimateAI

Benign

0.46

PROVEAN

Benign

0.12

REVEL

Benign

0.062

Sift

Benign

0.088

Sift4G

Benign

0.14

Polyphen

0.95

Vest4

0.12

MutPred

0.50

Gain of sheet (P = 0.0344)

MVP

0.43

MPC

0.43

ClinPred

0.74

GERP RS

4.4

PromoterAI

-0.021

Neutral

(source)

Varity_R

0.25

gMVP

0.70

Mutation Taster

=84/16

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over