17-800802-T-G

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.*147A>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 0.25 in 454,240 control chromosomes in the GnomAD database, including 14,868 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4459 hom., cov: 32)
  • Exomes 𝑓: 0.26 (10409 hom.)
• Consequence: NXN NM_022463.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.64

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=-0.48).
• BP6: Variant 17-800802-T-G is Benign according to our data. Variant chr17-800802-T-G is described in ClinVar as [Benign]. Clinvar id is 1259938.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NXN	NM_022463.5	c.*147A>C		3_prime_UTR_variant	8/8	ENST00000336868.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NXN	ENST00000336868.8	c.*147A>C		3_prime_UTR_variant	8/8	1	NM_022463.5	P1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 34763 AN: 150402 Hom.: 4452 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.202

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.256

GnomAD4 exome AF: 0.259 AC: 78685 AN: 303720 Hom.: 10409 Cov.: 5 AF XY: 0.260 AC XY: 40258 AN XY: 154618

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.298

Gnomad4 ASJ exome AF: 0.272

Gnomad4 EAS exome AF: 0.135

Gnomad4 SAS exome AF: 0.213

Gnomad4 FIN exome AF: 0.303

Gnomad4 NFE exome AF: 0.275

Gnomad4 OTH exome AF: 0.246

GnomAD4 genome AF: 0.231 AC: 34786 AN: 150520 Hom.: 4459 Cov.: 32 AF XY: 0.235 AC XY: 17245 AN XY: 73490

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.262

Alfa AF: 0.258 Hom.: 1056

Bravo AF: 0.226

Asia WGS AF: 0.201 AC: 699 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	-0.48
Cadd	Benign	12
Dann	Benign	0.87

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: rs655377; hg19: chr17-704042; COSMIC: COSV61094639;