Variant 4-177335746-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018248.3(NEIL3):c.337A>T(p.Asn113Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

NEIL3
NM_018248.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22089389).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEIL3	NM_018248.3 link	c.337A>T	p.Asn113Tyr	missense_variant	3/10	ENST00000264596.4	NP_060718.3	Q8TAT5
NEIL3	XM_047415894.1 link	c.337A>T	p.Asn113Tyr	missense_variant	3/12		XP_047271850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NEIL3	ENST00000264596.4 link	c.337A>T	p.Asn113Tyr	missense_variant	3/10	1	NM_018248.3	ENSP00000264596.3	Q8TAT5
NEIL3	ENST00000513321.1 link	n.*23A>T		non_coding_transcript_exon_variant	2/4	1		ENSP00000424735.1	D6RAV1
NEIL3	ENST00000513321.1 link	n.*23A>T		3_prime_UTR_variant	2/4	1		ENSP00000424735.1	D6RAV1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1445940

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718462

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.04e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 16, 2024

The c.337A>T (p.N113Y) alteration is located in exon 3 (coding exon 3) of the NEIL3 gene. This alteration results from a A to T substitution at nucleotide position 337, causing the asparagine (N) at amino acid position 113 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.13

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.62

M_CAP

Benign

0.013

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.4

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.055

Sift

Uncertain

0.021

Sift4G

Uncertain

0.030

Polyphen

0.67

Vest4

0.41

MutPred

0.46

Loss of methylation at K110 (P = 0.0601);

MVP

0.55

MPC

0.38

ClinPred

0.46

GERP RS

2.8

Varity_R

0.085

gMVP

0.28

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over