Genetic Variant NM_018248.3:c.145G>T (chr4-177310098-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.145G>T(p.Val49Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NEIL3
NM_018248.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.658

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=0.113188565).

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.145G>T	p.Val49Phe	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.145G>T	p.Val49Phe	missense	Exon 1 of 10	ENSP00000264596.3	Q8TAT5
NEIL3	ENST00000513321.1	TSL:1	n.145G>T		non_coding_transcript_exon	Exon 1 of 4	ENSP00000424735.1	D6RAV1
NEIL3	ENST00000905043.1		c.145G>T	p.Val49Phe	missense	Exon 1 of 10	ENSP00000575102.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1433398

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

712318

African (AFR)

AF:

0.00

AC:

AN:

31722

American (AMR)

AF:

0.00

AC:

AN:

39262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25132

East Asian (EAS)

AF:

0.00

AC:

AN:

37664

South Asian (SAS)

AF:

0.00

AC:

AN:

82862

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52466

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4554

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1100658

Other (OTH)

AF:

0.00

AC:

AN:

59078

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000313

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

5.6

(source)

DANN

Benign

0.50

DEOGEN2

Benign

0.031

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.33

M_CAP

Benign

0.0040

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

PhyloP100

-0.66

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.39

REVEL

Benign

0.067

Sift

Benign

0.74

Sift4G

Benign

0.72

Polyphen

0.96

Vest4

0.12

MutPred

0.47

Loss of glycosylation at S45 (P = 0.0672)

MVP

0.20

MPC

0.17

ClinPred

0.16

GERP RS

-0.63

PromoterAI

-0.018

Neutral

(source)

Varity_R

0.049

gMVP

0.52

Mutation Taster

=98/2

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over