rs4307650

Variant names:

• chr10-103200095-C-A
• rs4307650
• ENST00000674696.1:c.-24-25113G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-103200095-C-A
• chr10-103200095-C-G
• chr10-103200095-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000674696.1(NT5C2):​c.-24-25113G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,042 control chromosomes in the GnomAD database, including 12,871 homozygotes. 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: 𝑓 0.41 (12871 hom., cov: 32)
• Consequence: NT5C2 ENST00000674696.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285
• Publications: 13 publications found

Genes affected

NT5C2 (HGNC:8022): (5'-nucleotidase, cytosolic II) This gene encodes a hydrolase that serves as an important role in cellular purine metabolism by acting primarily on inosine 5'-monophosphate and other purine nucleotides. [provided by RefSeq, Oct 2011]

NT5C2 Gene-Disease associations (from GenCC):

• complex hereditary spastic paraplegia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hereditary spastic paraplegia 45

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000674696.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C2	ENST00000674696.1		c.-24-25113G>T		intron	N/A	ENSP00000502679.1	P49902-1
	NT5C2	ENST00000675326.1		c.-168-18767G>T		intron	N/A	ENSP00000502205.1	P49902-1
	NT5C2	ENST00000676428.1		c.-117-2238G>T		intron	N/A	ENSP00000501689.1	P49902-1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 62022 AN: 151924 Hom.: 12853 Cov.: 32

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.419

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.408 AC: 62086 AN: 152042 Hom.: 12871 Cov.: 32 AF XY: 0.407 AC XY: 30217 AN XY: 74308

African (AFR) AF: 0.390 AC: 16172 AN: 41476

American (AMR) AF: 0.402 AC: 6139 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1514 AN: 3470

East Asian (EAS) AF: 0.529 AC: 2734 AN: 5164

South Asian (SAS) AF: 0.444 AC: 2141 AN: 4820

European-Finnish (FIN) AF: 0.367 AC: 3873 AN: 10556

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28176 AN: 67964

Other (OTH) AF: 0.422 AC: 892 AN: 2114

Alfa AF: 0.387 Hom.: 5801

Bravo AF: 0.410

Asia WGS AF: 0.445 AC: 1544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.62
DANN	Benign	0.54
PhyloP100		-0.28

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4307650;

hg19: chr10-104959852;