4-177335824-T-TA

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000264596.4(NEIL3):​c.413+2_413+3insA variant causes a splice region, intron change. The variant allele was found at a frequency of 0.044 in 1,525,280 control chromosomes in the GnomAD database, including 3,038 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.044 (309 hom., cov: 32)
  • Exomes 𝑓: 0.044 (2729 hom.)
• Consequence: NEIL3 ENST00000264596.4 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 Benign. Variant got -10 ACMG points.

• BP6: Variant 4-177335824-T-TA is Benign according to our data. Variant chr4-177335824-T-TA is described in ClinVar as [Benign]. Clinvar id is 2688512.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL3	NM_018248.3	c.413+10dupA		intron_variant	Intron 3 of 9	ENST00000264596.4	NP_060718.3
NEIL3	XM_047415894.1	c.413+10dupA		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+2_413+3insA		splice_region_variant, intron_variant	Intron 3 of 9	1	NM_018248.3	ENSP00000264596.3
NEIL3	ENST00000513321.1	n.*99+2_*99+3insA		splice_region_variant, intron_variant	Intron 2 of 3	1		ENSP00000424735.1

Frequencies

GnomAD3 genomes AF: 0.0442 AC: 6707 AN: 151886 Hom.: 309 Cov.: 32

Gnomad AFR AF: 0.0334

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0753

Gnomad ASJ AF: 0.00867

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.0657

Gnomad FIN AF: 0.0175

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0308

Gnomad OTH AF: 0.0500

GnomAD3 exomes AF: 0.0595 AC: 11059 AN: 185788 Hom.: 753 AF XY: 0.0554 AC XY: 5644 AN XY: 101834

Gnomad AFR exome AF: 0.0326

Gnomad AMR exome AF: 0.113

Gnomad ASJ exome AF: 0.0120

Gnomad EAS exome AF: 0.274

Gnomad SAS exome AF: 0.0575

Gnomad FIN exome AF: 0.0159

Gnomad NFE exome AF: 0.0324

Gnomad OTH exome AF: 0.0492

GnomAD4 exome AF: 0.0440 AC: 60469 AN: 1373278 Hom.: 2729 Cov.: 31 AF XY: 0.0435 AC XY: 29495 AN XY: 678336

Gnomad4 AFR exome AF: 0.0311

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.0113

Gnomad4 EAS exome AF: 0.292

Gnomad4 SAS exome AF: 0.0518

Gnomad4 FIN exome AF: 0.0165

Gnomad4 NFE exome AF: 0.0353

Gnomad4 OTH exome AF: 0.0508

GnomAD4 genome AF: 0.0442 AC: 6716 AN: 152002 Hom.: 309 Cov.: 32 AF XY: 0.0447 AC XY: 3322 AN XY: 74288

Gnomad4 AFR AF: 0.0334

Gnomad4 AMR AF: 0.0752

Gnomad4 ASJ AF: 0.00867

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.0656

Gnomad4 FIN AF: 0.0175

Gnomad4 NFE AF: 0.0308

Gnomad4 OTH AF: 0.0518

Bravo AF: 0.0526

Asia WGS AF: 0.160 AC: 555 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 20% of patients studied by a panel of primary immunodeficiencies. Number of patients: 18. Only high quality variants are reported. -

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;