chr4-177335824-TA-T

Variant names:

• chr4-177335824-TA-T
• rs35737622
• NM_018248.3:c.413+10delA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000264596.4(NEIL3):​c.413+3delA variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00000947 in 1,373,418 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000095 (0 hom.)
• Consequence: NEIL3 ENST00000264596.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.03

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL3	NM_018248.3	c.413+10delA		intron_variant	Intron 3 of 9	ENST00000264596.4	NP_060718.3
NEIL3	XM_047415894.1	c.413+10delA		intron_variant	Intron 3 of 11		XP_047271850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEIL3	ENST00000264596.4	c.413+3delA		splice_region_variant, intron_variant	Intron 3 of 9	1	NM_018248.3	ENSP00000264596.3
NEIL3	ENST00000513321.1	n.*99+3delA		splice_region_variant, intron_variant	Intron 2 of 3	1		ENSP00000424735.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000947 AC: 13 AN: 1373418 Hom.: 0 Cov.: 31 AF XY: 0.0000103 AC XY: 7 AN XY: 678414

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000451

Gnomad4 EAS exome AF: 0.0000796

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000198

Gnomad4 NFE exome AF: 0.00000652

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs35737622; hg19: chr4-178256978;