rs745438856

Variant names:

• chr15-75352229-C-G
• NM_024608.4:c.553C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-75352229-C-G
• chr15-75352229-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_024608.4(NEIL1):​c.553C>G​(p.Arg185Gly) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000274 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 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: 0.0000027 (0 hom.)
• Consequence: NEIL1 NM_024608.4 missense, splice_region
• Scores: Splicing: ADA: 0.8048
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.12

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.949

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL1	NM_024608.4	c.553C>G	p.Arg185Gly	missense_variant, splice_region_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.553C>G	p.Arg185Gly	missense_variant, splice_region_variant	Exon 3 of 10	2	NM_024608.4	ENSP00000347170.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461878 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000360

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	0.81
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	34
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;T;T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.94	.;.;D
M_CAP	Uncertain	0.088	D
MetaRNN	Pathogenic	0.95	D;D;D
MetaSVM	Benign	-0.69	T
MutationAssessor	Pathogenic	3.8	H;H;H
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-5.6	D;D;D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.94
MutPred		0.81		Loss of stability (P = 0.0707);Loss of stability (P = 0.0707);Loss of stability (P = 0.0707);
MVP		0.57
MPC		0.78
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.94
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.80
dbscSNV1_RF	Benign	0.49
SpliceAI score (max)		0.64		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.64		Position offset: -5

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: chr15-75644570;