chr15-73570346-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_012428.4(NPTN):​c.918G>T​(p.Gln306His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

NPTN
NM_012428.4 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.341
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2643259).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NPTNNM_012428.4 linkuse as main transcriptc.918G>T p.Gln306His missense_variant 6/9 ENST00000345330.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NPTNENST00000345330.9 linkuse as main transcriptc.918G>T p.Gln306His missense_variant 6/91 NM_012428.4 P4Q9Y639-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000801
AC:
2
AN:
249808
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135164
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461798
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727202
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000671
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 23, 2024The c.918G>T (p.Q306H) alteration is located in exon 6 (coding exon 6) of the NPTN gene. This alteration results from a G to T substitution at nucleotide position 918, causing the glutamine (Q) at amino acid position 306 to be replaced by a histidine (H). 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
Benign
0.17
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.10
T;.;T;.;.;T
Eigen
Benign
-0.17
Eigen_PC
Benign
-0.16
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Uncertain
0.89
D;D;D;D;D;D
M_CAP
Benign
0.031
D
MetaRNN
Benign
0.26
T;T;T;T;T;T
MetaSVM
Benign
-0.75
T
MutationAssessor
Benign
0.90
L;.;.;.;L;.
MutationTaster
Benign
0.91
D;D;D;D;D;D;D
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-1.6
N;N;N;N;N;N
REVEL
Benign
0.19
Sift
Uncertain
0.0070
D;D;D;D;D;D
Sift4G
Uncertain
0.017
D;D;.;D;D;.
Polyphen
0.96
P;.;.;P;P;.
Vest4
0.14
MutPred
0.60
Gain of disorder (P = 0.116);.;.;.;Gain of disorder (P = 0.116);.;
MVP
0.53
MPC
0.82
ClinPred
0.36
T
GERP RS
-0.48
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.11
gMVP
0.59

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1159772182; hg19: chr15-73862687; API