chr4-177310003-G-T

Variant names:

• chr4-177310003-G-T
• rs200543340
• NM_018248.3:c.50G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NEIL3 NM_018248.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207

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]

ACMG classification

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=0.091340184).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL3	NM_018248.3	c.50G>T	p.Arg17Leu	missense_variant	Exon 1 of 10	ENST00000264596.4	NP_060718.3
NEIL3	XM_047415894.1	c.50G>T	p.Arg17Leu	missense_variant	Exon 1 of 12		XP_047271850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEIL3	ENST00000264596.4	c.50G>T	p.Arg17Leu	missense_variant	Exon 1 of 10	1	NM_018248.3	ENSP00000264596.3
NEIL3	ENST00000513321.1	n.50G>T		non_coding_transcript_exon_variant	Exon 1 of 4	1		ENSP00000424735.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000810 AC: 2 AN: 246908 Hom.: 0 AF XY: 0.0000149 AC XY: 2 AN XY: 134188

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 SAS exome AF: 0.0000330

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000168

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458470 Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2 AN XY: 725552

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.095
Sift	Benign	0.051	T
Sift4G	Uncertain	0.016	D
Polyphen		0.28	B
Vest4		0.22
MutPred		0.47		Loss of MoRF binding (P = 0.0124);
MVP		0.41
MPC		0.19
ClinPred		0.64	D
GERP RS		0.30
Varity_R		0.089
gMVP		0.61

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

Other links and lift over

dbSNP: rs200543340; hg19: chr4-178231157;