chr22-38821996-G-A

Position:

• chr22-38821996-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014293.4(NPTXR):​c.*613C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 146,452 control chromosomes in the GnomAD database, including 2,181 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 0.17 (2141 hom., cov: 29)
  • Exomes 𝑓: 0.11 (40 hom.)
• Consequence: NPTXR NM_014293.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.558

Genes affected

NPTXR (HGNC:7954): (neuronal pentraxin receptor) This gene encodes a protein similar to the rat neuronal pentraxin receptor. The rat pentraxin receptor is an integral membrane protein that is thought to mediate neuronal uptake of the snake venom toxin, taipoxin, and its transport into the synapses. Studies in rat indicate that translation of this mRNA initiates at a non-AUG (CUG) codon. This may also be true for mouse and human, based on strong sequence conservation amongst these species. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPTXR	NM_014293.4	c.*613C>T		3_prime_UTR_variant	5/5	ENST00000333039.4	NP_055108.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPTXR	ENST00000333039	c.*613C>T		3_prime_UTR_variant	5/5	1	NM_014293.4	ENSP00000327545.3

Frequencies

GnomAD3 genomes AF: 0.174 AC: 24641 AN: 141870 Hom.: 2138 Cov.: 29

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.0275

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.112 AC: 498 AN: 4454 Hom.: 40 Cov.: 0 AF XY: 0.110 AC XY: 265 AN XY: 2408

Gnomad4 AFR exome AF: 0.0238

Gnomad4 AMR exome AF: 0.0689

Gnomad4 ASJ exome AF: 0.0625

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0878

Gnomad4 FIN exome AF: 0.159

Gnomad4 NFE exome AF: 0.131

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.174 AC: 24658 AN: 141998 Hom.: 2141 Cov.: 29 AF XY: 0.177 AC XY: 12096 AN XY: 68258

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.0272

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.189

Alfa AF: 0.162 Hom.: 2073

Bravo AF: 0.157

Asia WGS AF: 0.0910 AC: 318 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	12
DANN	Benign	0.72

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: rs8140217; hg19: chr22-39218001;