10-103091528-G-T

Variant names:

• chr10-103091528-G-T
• rs10883830
• NM_001351169.2:c.1211+36C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001351169.2(NT5C2):​c.1211+36C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000736 in 1,359,054 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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.1211+36C>A		intron	N/A	NP_001338098.1
	NT5C2	NM_001351170.2		c.1235+36C>A		intron	N/A	NP_001338099.1
	NT5C2	NM_001351171.2		c.1235+36C>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+36C>A		intron	N/A	ENSP00000383960.3
	NT5C2	ENST00000343289.9	TSL:1	c.1211+36C>A		intron	N/A	ENSP00000339479.5
	NT5C2	ENST00000674860.1		c.1235+36C>A		intron	N/A	ENSP00000502816.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.36e-7 AC: 1 AN: 1359054 Hom.: 0 Cov.: 20 AF XY: 0.00000147 AC XY: 1 AN XY: 682072

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31234

American (AMR) AF: 0.00 AC: 0 AN: 43942

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25418

East Asian (EAS) AF: 0.00 AC: 0 AN: 39070

South Asian (SAS) AF: 0.00 AC: 0 AN: 83130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5304

European-Non Finnish (NFE) AF: 9.80e-7 AC: 1 AN: 1020894

Other (OTH) AF: 0.00 AC: 0 AN: 56880

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.37
PhyloP100		0.36

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: rs10883830; hg19: chr10-104851285;