Genetic Variant NPTN:c.-350G>A (chr15-73633565-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000351217.10(NPTN):c.-350G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0561 in 225,142 control chromosomes in the GnomAD database, including 370 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.057 ( 259 hom., cov: 32)

Exomes 𝑓: 0.055 ( 111 hom. )

Consequence

NPTN
ENST00000351217.10 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.297

Publications

1 publications found

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]

NPTN links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000351217.10, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.084 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000351217.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NPTN	NM_012428.4	MANE Select	c.-350G>A	upstream_gene	N/A	NP_036560.1	Q9Y639-2
NPTN	NM_001161363.2		c.-350G>A	upstream_gene	N/A	NP_001154835.1	Q9Y639-5
NPTN	NM_017455.4		c.-350G>A	upstream_gene	N/A	NP_059429.1	Q9Y639-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NPTN	ENST00000351217.10	TSL:1	c.-350G>A	5_prime_UTR	Exon 1 of 8	ENSP00000342958.6	Q9Y639-1
NPTN	ENST00000345330.9	TSL:1 MANE Select	c.-350G>A	upstream_gene	N/A	ENSP00000290401.4	Q9Y639-2
NPTN	ENST00000970036.1		c.-350G>A	upstream_gene	N/A	ENSP00000640095.1

Frequencies

GnomAD3 genomes

AF:

0.0567

AC:

8628

AN:

152170

Hom.:

257

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0677

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0403

Gnomad ASJ

AF:

0.0493

Gnomad EAS

AF:

0.0690

Gnomad SAS

AF:

0.0916

Gnomad FIN

AF:

0.0631

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0508

Gnomad OTH

AF:

0.0517

GnomAD4 exome

AF:

0.0546

AC:

3981

AN:

72854

Hom.:

111

Cov.:

AF XY:

0.0548

AC XY:

2059

AN XY:

37570

show subpopulations

African (AFR)

AF:

0.0846

AC:

212

AN:

2506

American (AMR)

AF:

0.0413

AC:

AN:

1888

Ashkenazi Jewish (ASJ)

AF:

0.0498

AC:

152

AN:

3050

East Asian (EAS)

AF:

0.0604

AC:

383

AN:

6346

South Asian (SAS)

AF:

0.0683

AC:

160

AN:

2342

European-Finnish (FIN)

AF:

0.0683

AC:

289

AN:

4230

Middle Eastern (MID)

AF:

0.0273

AC:

AN:

440

European-Non Finnish (NFE)

AF:

0.0515

AC:

2429

AN:

47150

Other (OTH)

AF:

0.0543

AC:

266

AN:

4902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

182

364

547

729

911

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0568

AC:

8644

AN:

152288

Hom.:

259

Cov.:

AF XY:

0.0575

AC XY:

4283

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0678

AC:

2819

AN:

41564

American (AMR)

AF:

0.0402

AC:

616

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0493

AC:

171

AN:

3466

East Asian (EAS)

AF:

0.0692

AC:

358

AN:

5174

South Asian (SAS)

AF:

0.0910

AC:

440

AN:

4834

European-Finnish (FIN)

AF:

0.0631

AC:

669

AN:

10604

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0508

AC:

3453

AN:

68024

Other (OTH)

AF:

0.0531

AC:

112

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

433

865

1298

1730

2163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

294

392

490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0193

Hom.:

Bravo

AF:

0.0541

Asia WGS

AF:

0.0990

AC:

344

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

-0.30

PromoterAI

-0.14

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over