chr10-103091544-G-T

Variant names:

• chr10-103091544-G-T
• rs17094683
• NM_001351169.2:c.1211+20C>A

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.1235+20C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0944 in 1,594,886 control chromosomes in the GnomAD database, including 9,311 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.094 (881 hom., cov: 33)
  • Exomes 𝑓: 0.094 (8430 hom.)
• Consequence: NT5C2 NM_001351170.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.41
• Publications: 24 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=-0.74).
• BP6: Variant 10-103091544-G-T is Benign according to our data. Variant chr10-103091544-G-T is described in ClinVar as Benign. ClinVar VariationId is 380885.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C2	NM_001351169.2	MANE Select	c.1211+20C>A		intron	N/A	NP_001338098.1
	NT5C2	NM_001351170.2		c.1235+20C>A		intron	N/A	NP_001338099.1
	NT5C2	NM_001351171.2		c.1235+20C>A		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.1211+20C>A		intron	N/A	ENSP00000383960.3
	NT5C2	ENST00000343289.9	TSL:1	c.1211+20C>A		intron	N/A	ENSP00000339479.5
	NT5C2	ENST00000874311.1		c.1427+20C>A		intron	N/A	ENSP00000544370.1

Frequencies

GnomAD3 genomes AF: 0.0940 AC: 14298 AN: 152144 Hom.: 875 Cov.: 33

Gnomad AFR AF: 0.0594

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.0748

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0899

Gnomad OTH AF: 0.102

GnomAD2 exomes AF: 0.127 AC: 31716 AN: 248884 AF XY: 0.127

Gnomad AFR exome AF: 0.0576

Gnomad AMR exome AF: 0.207

Gnomad ASJ exome AF: 0.0760

Gnomad EAS exome AF: 0.274

Gnomad FIN exome AF: 0.0783

Gnomad NFE exome AF: 0.0867

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.0944 AC: 136209 AN: 1442624 Hom.: 8430 Cov.: 28 AF XY: 0.0973 AC XY: 69948 AN XY: 718868

African (AFR) AF: 0.0519 AC: 1708 AN: 32934

American (AMR) AF: 0.203 AC: 8969 AN: 44080

Ashkenazi Jewish (ASJ) AF: 0.0749 AC: 1943 AN: 25930

East Asian (EAS) AF: 0.262 AC: 10350 AN: 39494

South Asian (SAS) AF: 0.196 AC: 16668 AN: 85072

European-Finnish (FIN) AF: 0.0777 AC: 4142 AN: 53290

Middle Eastern (MID) AF: 0.0871 AC: 487 AN: 5594

European-Non Finnish (NFE) AF: 0.0784 AC: 86018 AN: 1096530

Other (OTH) AF: 0.0992 AC: 5924 AN: 59700

GnomAD4 genome AF: 0.0940 AC: 14318 AN: 152262 Hom.: 881 Cov.: 33 AF XY: 0.0961 AC XY: 7157 AN XY: 74460

African (AFR) AF: 0.0595 AC: 2473 AN: 41552

American (AMR) AF: 0.138 AC: 2109 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0700 AC: 243 AN: 3472

East Asian (EAS) AF: 0.278 AC: 1442 AN: 5178

South Asian (SAS) AF: 0.183 AC: 882 AN: 4826

European-Finnish (FIN) AF: 0.0748 AC: 793 AN: 10608

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0899 AC: 6117 AN: 68016

Other (OTH) AF: 0.105 AC: 222 AN: 2114

Alfa AF: 0.0802 Hom.: 179

Bravo AF: 0.0977

Asia WGS AF: 0.196 AC: 678 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary spastic paraplegia 45 (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.5
DANN	Benign	0.65
PhyloP100		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17094683; hg19: chr10-104851301;