chr22-38818769-G-T

Position:

• chr22-38818769-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_014293.4(NPTXR):​c.*3840C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,184 control chromosomes in the GnomAD database, including 1,980 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 0.16 (1979 hom., cov: 32)
  • Exomes 𝑓: 0.11 (1 hom.)
• Consequence: NPTXR NM_014293.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.610

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPTXR	NM_014293.4	c.*3840C>A		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.*3840C>A		3_prime_UTR_variant	5/5	1	NM_014293.4	ENSP00000327545.3

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23653 AN: 151906 Hom.: 1980 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.113 AC: 18 AN: 160 Hom.: 1 Cov.: 0 AF XY: 0.105 AC XY: 12 AN XY: 114

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.143

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.156 AC: 23646 AN: 152024 Hom.: 1979 Cov.: 32 AF XY: 0.158 AC XY: 11735 AN XY: 74330

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.173

Alfa AF: 0.170 Hom.: 2100

Bravo AF: 0.146

Asia WGS AF: 0.123 AC: 430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	10
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7288826; hg19: chr22-39214774;