17-928427-C-T

Variant names:

• chr17-928427-C-T
• rs2360111
• NM_022463.5:c.360+50892G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022463.5(NXN):​c.360+50892G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,050 control chromosomes in the GnomAD database, including 9,869 homozygotes. 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: 𝑓 0.35 (9869 hom., cov: 32)
• Consequence: NXN NM_022463.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.646
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• robinow syndrome, autosomal recessive 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal recessive Robinow syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NXN	NM_022463.5	c.360+50892G>A		intron_variant	Intron 1 of 7	ENST00000336868.8	NP_071908.2
NXN	XM_005256756.5	c.360+50892G>A		intron_variant	Intron 1 of 6		XP_005256813.1
NXN	XM_017024949.2	c.360+50892G>A		intron_variant	Intron 1 of 5		XP_016880438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NXN	ENST00000336868.8	c.360+50892G>A		intron_variant	Intron 1 of 7	1	NM_022463.5	ENSP00000337443.3
NXN	ENST00000571338.1	n.389+1236G>A		intron_variant	Intron 1 of 2	4
NXN	ENST00000575171.1	n.31+50892G>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52779 AN: 151930 Hom.: 9868 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.372

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.347 AC: 52809 AN: 152050 Hom.: 9869 Cov.: 32 AF XY: 0.346 AC XY: 25705 AN XY: 74300

African (AFR) AF: 0.201 AC: 8341 AN: 41500

American (AMR) AF: 0.387 AC: 5906 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1298 AN: 3466

East Asian (EAS) AF: 0.471 AC: 2428 AN: 5158

South Asian (SAS) AF: 0.348 AC: 1675 AN: 4812

European-Finnish (FIN) AF: 0.372 AC: 3929 AN: 10568

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27942 AN: 67980

Other (OTH) AF: 0.370 AC: 780 AN: 2110

Alfa AF: 0.392 Hom.: 53112

Bravo AF: 0.346

Asia WGS AF: 0.386 AC: 1345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.5
DANN	Benign	0.62
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

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: rs2360111; hg19: chr17-831667;