17-803622-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_022463.5(NXN):c.1125+60C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 1,609,498 control chromosomes in the GnomAD database, including 141,510 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (18293 hom., cov: 33)
  • Exomes 𝑓: 0.41 (123217 hom.)
• Consequence: NXN NM_022463.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.385

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-803622-G-C is Benign according to our data. Variant chr17-803622-G-C is described in ClinVar as [Benign]. Clinvar id is 1179586.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NXN	NM_022463.5	c.1125+60C>G		intron_variant		ENST00000336868.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NXN	ENST00000336868.8	c.1125+60C>G		intron_variant		1	NM_022463.5	P1

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72962 AN: 151984 Hom.: 18257 Cov.: 33

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.472

GnomAD4 exome AF: 0.408 AC: 594339 AN: 1457396 Hom.: 123217 AF XY: 0.406 AC XY: 294382 AN XY: 725064

Gnomad4 AFR exome AF: 0.632

Gnomad4 AMR exome AF: 0.501

Gnomad4 ASJ exome AF: 0.420

Gnomad4 EAS exome AF: 0.326

Gnomad4 SAS exome AF: 0.348

Gnomad4 FIN exome AF: 0.504

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 0.419

GnomAD4 genome AF: 0.480 AC: 73048 AN: 152102 Hom.: 18293 Cov.: 33 AF XY: 0.484 AC XY: 36028 AN XY: 74372

Gnomad4 AFR AF: 0.620

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.355

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.475

Alfa AF: 0.453 Hom.: 2018

Bravo AF: 0.487

Asia WGS AF: 0.396 AC: 1379 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.4
Dann	Benign	0.24
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs598974; hg19: chr17-706862; COSMIC: COSV61095119;