chr17-80470890-C-A

Variant names:

• chr17-80470890-C-A
• NM_002522.4:c.1222G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_002522.4(NPTX1):​c.1222G>T​(p.Ala408Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A408T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NPTX1 NM_002522.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05

Genes affected

NPTX1 (HGNC:7952): (neuronal pentraxin 1) NPTX1 is a member of the neuronal pentraxin gene family. Neuronal pentraxin 1 is similar to the rat NP1 gene which encodes a binding protein for the snake venom toxin taipoxin. Human NPTX1 mRNA is exclusively localized to the nervous system. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a domain Pentraxin (PTX) (size 202) in uniprot entity NPTX1_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_002522.4
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1299707).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPTX1	NM_002522.4	c.1222G>T	p.Ala408Ser	missense_variant	Exon 5 of 5	ENST00000306773.5	NP_002513.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPTX1	ENST00000306773.5	c.1222G>T	p.Ala408Ser	missense_variant	Exon 5 of 5	1	NM_002522.4	ENSP00000307549.4
NPTX1	ENST00000571100.2	c.508G>T	p.Ala170Ser	missense_variant	Exon 4 of 4	4		ENSP00000511957.1
NPTX1	ENST00000535681.1	n.1824G>T		non_coding_transcript_exon_variant	Exon 3 of 4	2
NPTX1	ENST00000695485.1	n.645G>T		non_coding_transcript_exon_variant	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460862 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726534

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.050
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.36	N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.31	N
REVEL	Benign	0.073
Sift	Benign	0.43	T
Sift4G	Benign	0.98	T
Polyphen		0.015	B
Vest4		0.060
MutPred		0.52		Loss of sheet (P = 0.1398);
MVP		0.38
MPC		0.82
ClinPred		0.59	D
GERP RS		5.5
Varity_R		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-78444690;