chr17-80475556-T-G

Variant names:

• chr17-80475556-T-G
• rs772272561
• NM_002522.4:c.607A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002522.4(NPTX1):​c.607A>C​(p.Thr203Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. T203S) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: NPTX1 NM_002522.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.45
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23233119).

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.607A>C	p.Thr203Pro	missense	Exon 2 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.607A>C	p.Thr203Pro	missense	Exon 2 of 5	ENSP00000307549.4	Q15818
	NPTX1	ENST00000571100.2	TSL:4	c.-108A>C		5_prime_UTR	Exon 1 of 4	ENSP00000511957.1	A0A8Q3WL24
	NPTX1	ENST00000575212.1	TSL:4	n.396A>C		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152078 Hom.: 0 Cov.: 32

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152078 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74290

African (AFR) AF: 0.00 AC: 0 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68004

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

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.051
Eigen_PC	Benign	0.029
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.5
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.044
Sift	Benign	0.049	D
Sift4G	Benign	0.081	T
Polyphen		0.53	P
Vest4		0.31
MutPred		0.32		Loss of helix (P = 0.0237)
MVP		0.29
MPC		1.3
ClinPred		0.73	D
GERP RS		3.6
Varity_R		0.41

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: rs772272561; hg19: chr17-78449356;