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GeneBe

17-800961-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_022463.5(NXN):c.1296G>A(p.Pro432=) 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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 31 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NXNNM_022463.5 linkuse as main transcriptc.1296G>A p.Pro432= synonymous_variant 8/8 ENST00000336868.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NXNENST00000336868.8 linkuse as main transcriptc.1296G>A p.Pro432= synonymous_variant 8/81 NM_022463.5 P1Q6DKJ4-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0163
AC:
2479
AN:
151994
Hom.:
31
Cov.:
31
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.:
45
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.:
31
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0163
AC:
2477
AN:
152112
Hom.:
31
Cov.:
31
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.:
18
Bravo
AF:
0.0151
Asia WGS
AF:
0.00231
AC:
8
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 29, 2024- -

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.

Other links and lift over

dbSNP: rs56343681; hg19: chr17-704201; COSMIC: COSV61101586; API