chr17-80473250-C-G

Variant names:

• chr17-80473250-C-G
• rs140465326
• NM_002522.4:c.847G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_002522.4(NPTX1):​c.847G>C​(p.Val283Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,613,714 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: NPTX1 NM_002522.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.76
• Publications: 1 publications found

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]

NPTX1 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia 50

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal dominant cerebellar ataxia

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 12 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002522.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPTX1	NM_002522.4	MANE Select	c.847G>C	p.Val283Leu	missense	Exon 3 of 5	NP_002513.2	Q15818

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPTX1	ENST00000306773.5	TSL:1 MANE Select	c.847G>C	p.Val283Leu	missense	Exon 3 of 5	ENSP00000307549.4	Q15818
	NPTX1	ENST00000571100.2	TSL:4	c.133G>C	p.Val45Leu	missense	Exon 2 of 4	ENSP00000511957.1	A0A8Q3WL24
	NPTX1	ENST00000535681.1	TSL:2	n.1449G>C		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152264 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000360 AC: 9 AN: 249828 AF XY: 0.0000370

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000445

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000115 AC: 168 AN: 1461450 Hom.: 0 Cov.: 33 AF XY: 0.0000990 AC XY: 72 AN XY: 727046

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53010

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.000140 AC: 156 AN: 1111994

Other (OTH) AF: 0.0000828 AC: 5 AN: 60386

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152264 Hom.: 0 Cov.: 34 AF XY: 0.0000806 AC XY: 6 AN XY: 74396

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68056

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000113 Hom.: 0

Bravo AF: 0.0000604

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000576 AC: 7

EpiCase AF: 0.000218

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.2	L
PhyloP100		7.8
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.25
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.036	D
Polyphen		0.31	B
Vest4		0.85
MVP		0.24
MPC		1.6
ClinPred		0.35	T
GERP RS		4.3
Varity_R		0.90
Mutation Taster		=15/85	disease causing

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

Other links and lift over

dbSNP: rs140465326; hg19: chr17-78447050;