Variant 17-800961-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_022463.5(NXN):c.1296G>A(p.Pro432Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0209 in 1,481,678 control chromosomes in the GnomAD database, including 390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 31 hom., cov: 31)

Exomes 𝑓: 0.021 ( 359 hom. )

Consequence

NXN
NM_022463.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.00

Variant links:

Genes affected

NXN (HGNC:18008): (nucleoredoxin) This gene encodes a member of the thioredoxin superfamily, a group of small, multifunctional redox-active proteins. Members of this family are characterized by a conserved active motif called the thioredoxin fold that catalyzes disulfide bond formation and isomerization. The encoded protein acts a redox-dependent regulator of the Wnt signaling pathway and is involved in cell growth and differentiation. [provided by RefSeq, Sep 2015]

NXN links:

NXN (HGNC:):

NXN 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=-0.67).

BP6

Variant 17-800961-C-T is Benign according to our data. Variant chr17-800961-C-T is described in ClinVar as [Benign]. Clinvar id is 1632688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0163 (2477/152112) while in subpopulation NFE AF= 0.0264 (1794/67972). AF 95% confidence interval is 0.0254. There are 31 homozygotes in gnomad4. There are 1103 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NXN	NM_022463.5 linkuse as main transcript	c.1296G>A	p.Pro432Pro	synonymous_variant	8/8	ENST00000336868.8	NP_071908.2	Q6DKJ4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NXN	ENST00000336868.8 linkuse as main transcript	c.1296G>A	p.Pro432Pro	synonymous_variant	8/8	1	NM_022463.5	ENSP00000337443.3		Q6DKJ4-1

Frequencies

GnomAD3 genomes

AF:

0.0163

AC:

2479

AN:

151994

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00529

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.0145

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00415

Gnomad FIN

AF:

0.00962

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0264

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.0161

AC:

2838

AN:

176288

Hom.:

AF XY:

0.0160

AC XY:

1538

AN XY:

96186

show subpopulations

Gnomad AFR exome

AF:

0.00405

Gnomad AMR exome

AF:

0.0130

Gnomad ASJ exome

AF:

0.0133

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00590

Gnomad FIN exome

AF:

0.0110

Gnomad NFE exome

AF:

0.0241

Gnomad OTH exome

AF:

0.0174

GnomAD4 exome

AF:

0.0215

AC:

28532

AN:

1329566

Hom.:

359

Cov.:

AF XY:

0.0213

AC XY:

13909

AN XY:

653866

show subpopulations

Gnomad4 AFR exome

AF:

0.00294

Gnomad4 AMR exome

AF:

0.0133

Gnomad4 ASJ exome

AF:

0.0116

Gnomad4 EAS exome

AF:

0.0000301

Gnomad4 SAS exome

AF:

0.00623

Gnomad4 FIN exome

AF:

0.0117

Gnomad4 NFE exome

AF:

0.0247

Gnomad4 OTH exome

AF:

0.0180

GnomAD4 genome

AF:

0.0163

AC:

2477

AN:

152112

Hom.:

Cov.:

AF XY:

0.0148

AC XY:

1103

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00528

Gnomad4 AMR

AF:

0.0145

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00415

Gnomad4 FIN

AF:

0.00962

Gnomad4 NFE

AF:

0.0264

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.0192

Hom.:

Bravo

AF:

0.0151

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

4.4

DANN

Benign

0.66

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