rs7689099

Variant names:

• chr4-177335759-C-G
• rs7689099
• NM_018248.3:c.350C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-177335759-C-G
• chr4-177335759-C-A
• chr4-177335759-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018248.3(NEIL3):​c.350C>G​(p.Pro117Arg) variant causes a missense change. The variant allele was found at a frequency of 0.108 in 1,593,222 control chromosomes in the GnomAD database, including 10,147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.096 (816 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9331 hom.)
• Consequence: NEIL3 NM_018248.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.26
• Publications: 29 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0021573305).
• BP6: Variant 4-177335759-C-G is Benign according to our data. Variant chr4-177335759-C-G is described in ClinVar as Benign. ClinVar VariationId is 2688466.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

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.350C>G	p.Pro117Arg	missense	Exon 3 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.350C>G	p.Pro117Arg	missense	Exon 3 of 10	ENSP00000264596.3	Q8TAT5
	NEIL3	ENST00000513321.1	TSL:1	n.*36C>G		non_coding_transcript_exon	Exon 2 of 4	ENSP00000424735.1	D6RAV1
	NEIL3	ENST00000513321.1	TSL:1	n.*36C>G		3_prime_UTR	Exon 2 of 4	ENSP00000424735.1	D6RAV1

Frequencies

GnomAD3 genomes AF: 0.0959 AC: 14584 AN: 152032 Hom.: 815 Cov.: 32

Gnomad AFR AF: 0.0582

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.0258

Gnomad SAS AF: 0.0900

Gnomad FIN AF: 0.0577

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.130

GnomAD2 exomes AF: 0.106 AC: 25011 AN: 235846 AF XY: 0.107

Gnomad AFR exome AF: 0.0597

Gnomad AMR exome AF: 0.140

Gnomad ASJ exome AF: 0.178

Gnomad EAS exome AF: 0.0200

Gnomad FIN exome AF: 0.0650

Gnomad NFE exome AF: 0.120

Gnomad OTH exome AF: 0.129

GnomAD4 exome AF: 0.110 AC: 158254 AN: 1441072 Hom.: 9331 Cov.: 31 AF XY: 0.111 AC XY: 79245 AN XY: 715770

African (AFR) AF: 0.0611 AC: 1978 AN: 32354

American (AMR) AF: 0.139 AC: 5644 AN: 40694

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 4541 AN: 25378

East Asian (EAS) AF: 0.0241 AC: 946 AN: 39318

South Asian (SAS) AF: 0.0960 AC: 7838 AN: 81654

European-Finnish (FIN) AF: 0.0644 AC: 3418 AN: 53088

Middle Eastern (MID) AF: 0.222 AC: 1182 AN: 5322

European-Non Finnish (NFE) AF: 0.114 AC: 125898 AN: 1103822

Other (OTH) AF: 0.115 AC: 6809 AN: 59442

GnomAD4 genome AF: 0.0959 AC: 14589 AN: 152150 Hom.: 816 Cov.: 32 AF XY: 0.0948 AC XY: 7053 AN XY: 74398

African (AFR) AF: 0.0581 AC: 2414 AN: 41524

American (AMR) AF: 0.133 AC: 2037 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 608 AN: 3470

East Asian (EAS) AF: 0.0261 AC: 135 AN: 5176

South Asian (SAS) AF: 0.0903 AC: 436 AN: 4828

European-Finnish (FIN) AF: 0.0577 AC: 611 AN: 10588

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7915 AN: 67968

Other (OTH) AF: 0.129 AC: 273 AN: 2112

Alfa AF: 0.108 Hom.: 806

Bravo AF: 0.0986

TwinsUK AF: 0.119 AC: 440

ALSPAC AF: 0.109 AC: 422

ESP6500AA AF: 0.0609 AC: 268

ESP6500EA AF: 0.118 AC: 1013

ExAC AF: 0.103 AC: 12449

Asia WGS AF: 0.0660 AC: 229 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	D
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.79	T
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		5.3
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Benign	0.13
Sift	Uncertain	0.016	D
Sift4G	Benign	0.074	T
Polyphen		0.83	P
Vest4		0.28
MPC		0.26
ClinPred		0.063	T
GERP RS		5.1
Varity_R		0.38
gMVP		0.68
Mutation Taster		=83/17	polymorphism (auto)

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: rs7689099; hg19: chr4-178256913; COSMIC: COSV52809301;