rs3736922

Variant names:

• chr10-103090875-G-A
• rs3736922
• NM_001351169.2:c.1272+61C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-103090875-G-A
• chr10-103090875-G-C

Variant summary

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

The NM_001351170.2(NT5C2):​c.1296+61C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 1,595,100 control chromosomes in the GnomAD database, including 145,056 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (13997 hom., cov: 32)
  • Exomes 𝑓: 0.42 (131059 hom.)
• Consequence: NT5C2 NM_001351170.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0450
• Publications: 18 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=-0.59).
• BP6: Variant 10-103090875-G-A is Benign according to our data. Variant chr10-103090875-G-A is described in ClinVar as Benign. ClinVar VariationId is 1295358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351170.2. 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
	NT5C2	NM_001351169.2	MANE Select	c.1272+61C>T		intron	N/A	NP_001338098.1
	NT5C2	NM_001351170.2		c.1296+61C>T		intron	N/A	NP_001338099.1
	NT5C2	NM_001351171.2		c.1296+61C>T		intron	N/A	NP_001338100.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C2	ENST00000404739.8	TSL:1 MANE Select	c.1272+61C>T		intron	N/A	ENSP00000383960.3
	NT5C2	ENST00000343289.9	TSL:1	c.1272+61C>T		intron	N/A	ENSP00000339479.5
	NT5C2	ENST00000874311.1		c.1488+61C>T		intron	N/A	ENSP00000544370.1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64676 AN: 151862 Hom.: 13986 Cov.: 32

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.437

GnomAD4 exome AF: 0.424 AC: 612403 AN: 1443120 Hom.: 131059 Cov.: 26 AF XY: 0.426 AC XY: 306202 AN XY: 718820

African (AFR) AF: 0.391 AC: 12829 AN: 32830

American (AMR) AF: 0.431 AC: 18964 AN: 43994

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 12077 AN: 25936

East Asian (EAS) AF: 0.502 AC: 19883 AN: 39586

South Asian (SAS) AF: 0.466 AC: 39691 AN: 85236

European-Finnish (FIN) AF: 0.381 AC: 20297 AN: 53208

Middle Eastern (MID) AF: 0.465 AC: 2662 AN: 5722

European-Non Finnish (NFE) AF: 0.419 AC: 459968 AN: 1096924

Other (OTH) AF: 0.436 AC: 26032 AN: 59684

GnomAD4 genome AF: 0.426 AC: 64728 AN: 151980 Hom.: 13997 Cov.: 32 AF XY: 0.424 AC XY: 31500 AN XY: 74286

African (AFR) AF: 0.394 AC: 16346 AN: 41456

American (AMR) AF: 0.424 AC: 6472 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1661 AN: 3466

East Asian (EAS) AF: 0.560 AC: 2881 AN: 5148

South Asian (SAS) AF: 0.457 AC: 2201 AN: 4820

European-Finnish (FIN) AF: 0.380 AC: 4012 AN: 10560

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29733 AN: 67938

Other (OTH) AF: 0.440 AC: 928 AN: 2108

Alfa AF: 0.428 Hom.: 5454

Bravo AF: 0.428

Asia WGS AF: 0.473 AC: 1642 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	-0.59
CADD	Benign	4.0
DANN	Benign	0.51
PhyloP100		0.045
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: rs3736922; hg19: chr10-104850632; COSMIC: COSV58416851; COSMIC: COSV58416851;