17-800777-A-G

Position:

• chr17-800777-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022463.5(NXN):​c.*172T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 418,022 control chromosomes in the GnomAD database, including 73,688 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (25983 hom., cov: 32)
  • Exomes 𝑓: 0.60 (47705 hom.)
• Consequence: NXN NM_022463.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.94

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-800777-A-G is Benign according to our data. Variant chr17-800777-A-G is described in ClinVar as [Benign]. Clinvar id is 1274216.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NXN	NM_022463.5	c.*172T>C		3_prime_UTR_variant	8/8	ENST00000336868.8	NP_071908.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NXN	ENST00000336868.8	c.*172T>C		3_prime_UTR_variant	8/8	1	NM_022463.5	ENSP00000337443.3

Frequencies

GnomAD3 genomes AF: 0.579 AC: 88037 AN: 151932 Hom.: 25964 Cov.: 32

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.582

GnomAD4 exome AF: 0.596 AC: 158631 AN: 265972 Hom.: 47705 Cov.: 4 AF XY: 0.595 AC XY: 80636 AN XY: 135494

Gnomad4 AFR exome AF: 0.496

Gnomad4 AMR exome AF: 0.659

Gnomad4 ASJ exome AF: 0.591

Gnomad4 EAS exome AF: 0.677

Gnomad4 SAS exome AF: 0.507

Gnomad4 FIN exome AF: 0.663

Gnomad4 NFE exome AF: 0.583

Gnomad4 OTH exome AF: 0.590

GnomAD4 genome AF: 0.579 AC: 88099 AN: 152050 Hom.: 25983 Cov.: 32 AF XY: 0.584 AC XY: 43438 AN XY: 74344

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.630

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.775

Gnomad4 SAS AF: 0.514

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.586

Alfa AF: 0.582 Hom.: 3258

Bravo AF: 0.576

Asia WGS AF: 0.649 AC: 2254 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.7
DANN	Benign	0.48

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: rs2474695; hg19: chr17-704017; COSMIC: COSV61093600; COSMIC: COSV61093600;