Variant 10-103089711-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001351169.2(NT5C2):c.1647C>T(p.Asp549=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 1,611,386 control chromosomes in the GnomAD database, including 129,685 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 12616 hom., cov: 30)

Exomes 𝑓: 0.40 ( 117069 hom. )

Consequence

NT5C2
NM_001351169.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.259

Variant links:

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 links:

CNNM2 (HGNC:103): (cyclin and CBS domain divalent metal cation transport mediator 2) This gene encodes a member of the ancient conserved domain containing protein family. Members of this protein family contain a cyclin box motif and have structural similarity to the cyclins. The encoded protein may play an important role in magnesium homeostasis by mediating the epithelial transport and renal reabsorption of Mg2+. Mutations in this gene are associated with renal hypomagnesemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

CNNM2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 10-103089711-G-A is Benign according to our data. Variant chr10-103089711-G-A is described in ClinVar as [Benign]. Clinvar id is 380852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.259 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NT5C2	NM_001351169.2 linkuse as main transcript	c.1647C>T	p.Asp549=	synonymous_variant	19/19	ENST00000404739.8
CNNM2	NM_017649.5 linkuse as main transcript	c.*12531G>A		3_prime_UTR_variant	8/8	ENST00000369878.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NT5C2	ENST00000404739.8 linkuse as main transcript	c.1647C>T	p.Asp549=	synonymous_variant	19/19	1	NM_001351169.2	P1	P49902-1
CNNM2	ENST00000369878.9 linkuse as main transcript	c.*12531G>A		3_prime_UTR_variant	8/8	1	NM_017649.5	P4	Q9H8M5-1

Frequencies

GnomAD3 genomes

AF:

0.405

AC:

61405

AN:

151448

Hom.:

12605

Cov.:

show subpopulations

Gnomad AFR

AF:

0.388

Gnomad AMI

AF:

0.351

Gnomad AMR

AF:

0.403

Gnomad ASJ

AF:

0.431

Gnomad EAS

AF:

0.475

Gnomad SAS

AF:

0.427

Gnomad FIN

AF:

0.365

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.415

Gnomad OTH

AF:

0.416

GnomAD3 exomes

AF:

0.413

AC:

103054

AN:

249798

Hom.:

21314

AF XY:

0.414

AC XY:

55862

AN XY:

135000

show subpopulations

Gnomad AFR exome

AF:

0.385

Gnomad AMR exome

AF:

0.414

Gnomad ASJ exome

AF:

0.424

Gnomad EAS exome

AF:

0.475

Gnomad SAS exome

AF:

0.436

Gnomad FIN exome

AF:

0.367

Gnomad NFE exome

AF:

0.408

Gnomad OTH exome

AF:

0.412

GnomAD4 exome

AF:

0.399

AC:

582541

AN:

1459820

Hom.:

117069

Cov.:

AF XY:

0.400

AC XY:

290702

AN XY:

726162

show subpopulations

Gnomad4 AFR exome

AF:

0.385

Gnomad4 AMR exome

AF:

0.419

Gnomad4 ASJ exome

AF:

0.421

Gnomad4 EAS exome

AF:

0.413

Gnomad4 SAS exome

AF:

0.438

Gnomad4 FIN exome

AF:

0.366

Gnomad4 NFE exome

AF:

0.396

Gnomad4 OTH exome

AF:

0.407

GnomAD4 genome

AF:

0.405

AC:

61457

AN:

151566

Hom.:

12616

Cov.:

AF XY:

0.403

AC XY:

29827

AN XY:

74032

show subpopulations

Gnomad4 AFR

AF:

0.388

Gnomad4 AMR

AF:

0.403

Gnomad4 ASJ

AF:

0.431

Gnomad4 EAS

AF:

0.474

Gnomad4 SAS

AF:

0.426

Gnomad4 FIN

AF:

0.365

Gnomad4 NFE

AF:

0.415

Gnomad4 OTH

AF:

0.419

Alfa

AF:

0.410

Hom.:

16583

Bravo

AF:

0.407

Asia WGS

AF:

0.415

AC:

1441

AN:

3478

EpiCase

AF:

0.405

EpiControl

AF:

0.408

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 22, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Hereditary spastic paraplegia 45

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.41

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over