chr15-73570221-G-A

Position:

• chr15-73570221-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012428.4(NPTN):​c.1043C>T​(p.Ala348Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NPTN NM_012428.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.63

Genes affected

NPTN (HGNC:17867): (neuroplastin) This gene encodes a type I transmembrane protein belonging to the Ig superfamily. The protein is believed to be involved in cell-cell interactions or cell-substrate interactions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPTN	NM_012428.4	c.1043C>T	p.Ala348Val	missense_variant	6/9	ENST00000345330.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPTN	ENST00000345330.9	c.1043C>T	p.Ala348Val	missense_variant	6/9	1	NM_012428.4	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 23, 2024

The c.1043C>T (p.A348V) alteration is located in exon 6 (coding exon 6) of the NPTN gene. This alteration results from a C to T substitution at nucleotide position 1043, causing the alanine (A) at amino acid position 348 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.44	T;.;T;.;.
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D;D;D;D;D
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.73	D;D;D;D;D
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Uncertain	2.6	M;.;.;.;M
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.8	D;D;D;D;D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0010	D;D;D;D;D
Sift4G	Uncertain	0.0030	D;D;.;D;D
Polyphen		1.0	D;.;.;D;D
Vest4		0.33
MutPred		0.47		Loss of sheet (P = 0.0181);.;.;.;Loss of sheet (P = 0.0181);
MVP		0.66
MPC		0.92
ClinPred		0.97	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.65
gMVP		0.79

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: chr15-73862562;