rs10786737

Variant names:

• chr10-103097461-A-C
• rs10786737
• NM_001351169.2:c.688-87T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-103097461-A-C
• chr10-103097461-A-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001351169.2(NT5C2):​c.688-87T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,120,990 control chromosomes in the GnomAD database, including 14,275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1771 hom., cov: 32)
  • Exomes 𝑓: 0.16 (12504 hom.)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0780
• 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):

• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-103097461-A-C is Benign according to our data. Variant chr10-103097461-A-C is described in ClinVar as Benign. ClinVar VariationId is 667737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351169.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C2	NM_001351169.2	MANE Select	c.688-87T>G		intron	N/A	NP_001338098.1
	NT5C2	NM_001351170.2		c.712-87T>G		intron	N/A	NP_001338099.1
	NT5C2	NM_001351171.2		c.712-87T>G		intron	N/A	NP_001338100.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C2	ENST00000404739.8	TSL:1 MANE Select	c.688-87T>G		intron	N/A	ENSP00000383960.3
	NT5C2	ENST00000343289.9	TSL:1	c.688-87T>G		intron	N/A	ENSP00000339479.5
	NT5C2	ENST00000674728.1		n.*2081T>G		non_coding_transcript_exon	Exon 10 of 18	ENSP00000502126.1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22124 AN: 152118 Hom.: 1772 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.150

GnomAD4 exome AF: 0.157 AC: 152134 AN: 968756 Hom.: 12504 AF XY: 0.157 AC XY: 78757 AN XY: 500342

African (AFR) AF: 0.109 AC: 2588 AN: 23682

American (AMR) AF: 0.0916 AC: 3674 AN: 40114

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 4052 AN: 21802

East Asian (EAS) AF: 0.141 AC: 5232 AN: 37154

South Asian (SAS) AF: 0.154 AC: 11114 AN: 72176

European-Finnish (FIN) AF: 0.166 AC: 8591 AN: 51852

Middle Eastern (MID) AF: 0.130 AC: 620 AN: 4756

European-Non Finnish (NFE) AF: 0.162 AC: 109385 AN: 673404

Other (OTH) AF: 0.157 AC: 6878 AN: 43816

GnomAD4 genome AF: 0.145 AC: 22125 AN: 152234 Hom.: 1771 Cov.: 32 AF XY: 0.144 AC XY: 10696 AN XY: 74422

African (AFR) AF: 0.109 AC: 4536 AN: 41532

American (AMR) AF: 0.103 AC: 1571 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 697 AN: 3472

East Asian (EAS) AF: 0.191 AC: 989 AN: 5176

South Asian (SAS) AF: 0.160 AC: 773 AN: 4828

European-Finnish (FIN) AF: 0.160 AC: 1702 AN: 10608

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11404 AN: 68000

Other (OTH) AF: 0.150 AC: 317 AN: 2112

Alfa AF: 0.151 Hom.: 2400

Bravo AF: 0.138

Asia WGS AF: 0.148 AC: 515 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	13
DANN	Benign	0.59
PhyloP100		-0.078
Mutation Taster		=100/0	polymorphism (auto)

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: rs10786737; hg19: chr10-104857218; COSMIC: COSV58417684; COSMIC: COSV58417684;