NM_024608.4:c.449G>C

Variant names:

• chr15-75352125-G-C
• NM_024608.4:c.449G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024608.4(NEIL1):​c.449G>C​(p.Arg150Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,856 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NEIL1 NM_024608.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94

Genes affected

NEIL1 (HGNC:18448): (nei like DNA glycosylase 1) This gene is a member of the Nei endonuclease VIII-like gene family which encodes DNA glycosylases. The encoded enzyme participates in the DNA repair pathway by initiating base excision repair by removing damaged bases, primarily oxidized pyrimidines. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28020346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL1	NM_024608.4	c.449G>C	p.Arg150Pro	missense_variant	Exon 3 of 10	ENST00000355059.9	NP_078884.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEIL1	ENST00000355059.9	c.449G>C	p.Arg150Pro	missense_variant	Exon 3 of 10	2	NM_024608.4	ENSP00000347170.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461856 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;T;T;T
Eigen	Benign	-0.069
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.53	D
LIST_S2	Uncertain	0.92	.;D;.;D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.28	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.2	M;.;M;M
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.5	N;N;N;N
REVEL	Benign	0.25
Sift	Benign	0.038	D;T;D;D
Sift4G	Benign	0.088	T;T;T;T
Polyphen		0.88	P;.;P;P
Vest4		0.49
MutPred		0.59		Loss of helix (P = 0.028);Loss of helix (P = 0.028);Loss of helix (P = 0.028);Loss of helix (P = 0.028);
MVP		0.60
MPC		0.56
ClinPred		0.71	D
GERP RS		1.1
Varity_R		0.89
gMVP		0.90

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-75644466;