Genetic Variant NPTN:c.-226T>G (chr15-73633441-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000351217.10(NPTN):c.-226T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 397,134 control chromosomes in the GnomAD database, including 51,528 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 0.49 ( 18531 hom., cov: 32)

Exomes 𝑓: 0.52 ( 32997 hom. )

Consequence

NPTN
ENST00000351217.10 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.501

Publications

7 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 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.-226T>G	upstream_gene	N/A	NP_036560.1	Q9Y639-2
NPTN	NM_001161363.2		c.-226T>G	upstream_gene	N/A	NP_001154835.1	Q9Y639-5
NPTN	NM_017455.4		c.-226T>G	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.-226T>G	5_prime_UTR	Exon 1 of 8	ENSP00000342958.6	Q9Y639-1
NPTN	ENST00000970031.1		c.-226T>G	5_prime_UTR	Exon 1 of 6	ENSP00000640090.1
NPTN	ENST00000345330.9	TSL:1 MANE Select	c.-226T>G	upstream_gene	N/A	ENSP00000290401.4	Q9Y639-2

Frequencies

GnomAD3 genomes

AF:

0.490

AC:

74446

AN:

151802

Hom.:

18518

Cov.:

show subpopulations

Gnomad AFR

AF:

0.422

Gnomad AMI

AF:

0.597

Gnomad AMR

AF:

0.527

Gnomad ASJ

AF:

0.455

Gnomad EAS

AF:

0.531

Gnomad SAS

AF:

0.447

Gnomad FIN

AF:

0.528

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.519

Gnomad OTH

AF:

0.480

GnomAD4 exome

AF:

0.516

AC:

126459

AN:

245214

Hom.:

32997

Cov.:

AF XY:

0.514

AC XY:

65006

AN XY:

126554

show subpopulations

African (AFR)

AF:

0.424

AC:

2823

AN:

6662

American (AMR)

AF:

0.529

AC:

3607

AN:

6824

Ashkenazi Jewish (ASJ)

AF:

0.452

AC:

3998

AN:

8842

East Asian (EAS)

AF:

0.595

AC:

12874

AN:

21646

South Asian (SAS)

AF:

0.432

AC:

3745

AN:

8662

European-Finnish (FIN)

AF:

0.535

AC:

11008

AN:

20578

Middle Eastern (MID)

AF:

0.476

AC:

579

AN:

1216

European-Non Finnish (NFE)

AF:

0.516

AC:

79930

AN:

155020

Other (OTH)

AF:

0.501

AC:

7895

AN:

15764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

2822

5643

8465

11286

14108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

350

700

1050

1400

1750

<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:

0.490

AC:

74515

AN:

151920

Hom.:

18531

Cov.:

AF XY:

0.492

AC XY:

36534

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.422

AC:

17506

AN:

41462

American (AMR)

AF:

0.528

AC:

8066

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.455

AC:

1580

AN:

3470

East Asian (EAS)

AF:

0.532

AC:

2708

AN:

5092

South Asian (SAS)

AF:

0.446

AC:

2147

AN:

4816

European-Finnish (FIN)

AF:

0.528

AC:

5591

AN:

10580

Middle Eastern (MID)

AF:

0.449

AC:

132

AN:

294

European-Non Finnish (NFE)

AF:

0.519

AC:

35231

AN:

67908

Other (OTH)

AF:

0.480

AC:

1012

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1980

3960

5939

7919

9899

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

666

1332

1998

2664

3330

<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:

0.353

Hom.:

912

Bravo

AF:

0.489

Asia WGS

AF:

0.465

AC:

1621

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

-0.50

PromoterAI

-0.022

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