10-103193790-T-C

Variant names:

• chr10-103193790-T-C
• rs10748839
• ENST00000674696.1:c.-24-18808A>G

Variant summary

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

The ENST00000674696.1(NT5C2):​c.-24-18808A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,954 control chromosomes in the GnomAD database, including 12,958 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 (12958 hom., cov: 31)
• Consequence: NT5C2 ENST00000674696.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 21 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):

• hereditary spastic paraplegia 45

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C2	ENST00000674696.1	c.-24-18808A>G		intron_variant	Intron 1 of 17			ENSP00000502679.1
NT5C2	ENST00000675326.1	c.-168-12462A>G		intron_variant	Intron 1 of 18			ENSP00000502205.1
NT5C2	ENST00000676428.1	c.-25+3975A>G		intron_variant	Intron 2 of 18			ENSP00000501689.1

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62166 AN: 151838 Hom.: 12940 Cov.: 31

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.366

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: 0.410 AC: 62228 AN: 151954 Hom.: 12958 Cov.: 31 AF XY: 0.408 AC XY: 30281 AN XY: 74244

African (AFR) AF: 0.389 AC: 16138 AN: 41446

American (AMR) AF: 0.402 AC: 6142 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1515 AN: 3468

East Asian (EAS) AF: 0.559 AC: 2885 AN: 5162

South Asian (SAS) AF: 0.446 AC: 2150 AN: 4816

European-Finnish (FIN) AF: 0.366 AC: 3857 AN: 10526

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

European-Non Finnish (NFE) AF: 0.415 AC: 28206 AN: 67954

Other (OTH) AF: 0.423 AC: 889 AN: 2104

Alfa AF: 0.428 Hom.: 2379

Bravo AF: 0.411

Asia WGS AF: 0.468 AC: 1625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.6
DANN	Benign	0.39
PhyloP100		-1.3
PromoterAI		-0.033	Neutral

Splicing

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

Other links and lift over

dbSNP: rs10748839; hg19: chr10-104953547;