4-177309998-C-T

Variant names:

• chr4-177309998-C-T
• rs10013040
• NM_018248.3:c.45C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_018248.3(NEIL3):​c.45C>T​(p.Arg15Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R15R) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NEIL3 NM_018248.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.224
• Publications: 15 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=0.224 with no splicing effect.

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.45C>T	p.Arg15Arg	synonymous	Exon 1 of 10	NP_060718.3	Q8TAT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEIL3	ENST00000264596.4	TSL:1 MANE Select	c.45C>T	p.Arg15Arg	synonymous	Exon 1 of 10	ENSP00000264596.3	Q8TAT5
	NEIL3	ENST00000513321.1	TSL:1	n.45C>T		non_coding_transcript_exon	Exon 1 of 4	ENSP00000424735.1	D6RAV1
	NEIL3	ENST00000905043.1		c.45C>T	p.Arg15Arg	synonymous	Exon 1 of 10	ENSP00000575102.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457870 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 725202

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000301 AC: 1 AN: 33270

American (AMR) AF: 0.00 AC: 0 AN: 44446

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26030

East Asian (EAS) AF: 0.00 AC: 0 AN: 39460

South Asian (SAS) AF: 0.00 AC: 0 AN: 85850

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4692

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110614

Other (OTH) AF: 0.00 AC: 0 AN: 60178

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 10947

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	13
DANN	Benign	0.96
PhyloP100		0.22
PromoterAI		0.072	Neutral

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

Other links and lift over

dbSNP: rs10013040; hg19: chr4-178231152;