rs604229

Variant names:

• chr17-883588-C-T
• rs604229
• NM_022463.5:c.361-57510G>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.361-57510G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,272 control chromosomes in the GnomAD database, including 1,300 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 0.12 (1300 hom., cov: 33)
• Consequence: NXN NM_022463.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.498
• Publications: 2 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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NXN	NM_022463.5	c.361-57510G>A		intron_variant	Intron 1 of 7	ENST00000336868.8	NP_071908.2
NXN	XM_005256756.5	c.361-57510G>A		intron_variant	Intron 1 of 6		XP_005256813.1
NXN	XM_005256758.4	c.21+13298G>A		intron_variant	Intron 1 of 7		XP_005256815.1
NXN	XM_017024949.2	c.361-57510G>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.361-57510G>A		intron_variant	Intron 1 of 7	1	NM_022463.5	ENSP00000337443.3

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18508 AN: 152154 Hom.: 1302 Cov.: 33

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.00881

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.0927

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.0743

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.121 AC: 18496 AN: 152272 Hom.: 1300 Cov.: 33 AF XY: 0.127 AC XY: 9426 AN XY: 74456

African (AFR) AF: 0.170 AC: 7055 AN: 41554

American (AMR) AF: 0.159 AC: 2434 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0927 AC: 322 AN: 3472

East Asian (EAS) AF: 0.164 AC: 847 AN: 5180

South Asian (SAS) AF: 0.227 AC: 1094 AN: 4826

European-Finnish (FIN) AF: 0.133 AC: 1413 AN: 10608

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.0743 AC: 5057 AN: 68024

Other (OTH) AF: 0.114 AC: 241 AN: 2116

Alfa AF: 0.0906 Hom.: 2710

Bravo AF: 0.127

Asia WGS AF: 0.187 AC: 649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.3
DANN	Benign	0.70
PhyloP100		-0.50
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: rs604229; hg19: chr17-786828;