rs767730991

Variant names:

• chr4-177310044-G-C
• rs767730991
• NM_018248.3:c.91G>C

Your query was ambiguous. Multiple possible variants found:

• chr4-177310044-G-C
• chr4-177310044-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018248.3(NEIL3):​c.91G>C​(p.Ala31Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A31S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NEIL3 NM_018248.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.27
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

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

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.91G>C	p.Ala31Pro	missense	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.91G>C	p.Ala31Pro	missense	Exon 1 of 10	ENSP00000264596.3	Q8TAT5
	NEIL3	ENST00000513321.1	TSL:1	n.91G>C		non_coding_transcript_exon	Exon 1 of 4	ENSP00000424735.1	D6RAV1
	NEIL3	ENST00000905043.1		c.91G>C	p.Ala31Pro	missense	Exon 1 of 10	ENSP00000575102.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		3.3
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.26
Sift	Benign	0.047	D
Sift4G	Benign	0.12	T
Polyphen		1.0	D
Vest4		0.51
MutPred		0.54		Gain of glycosylation at A31 (P = 0.0575)
MVP		0.60
MPC		0.63
ClinPred		0.98	D
GERP RS		5.0
PromoterAI		0.0011	Neutral
Varity_R		0.77
gMVP		0.82
Mutation Taster		=59/41	polymorphism

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: rs767730991; hg19: chr4-178231198;