Genetic Variant ENST00000351217.10:c.-463delT (chr15-73633677-CA-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The ENST00000351217.10(NPTN):c.-463delT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 156,178 control chromosomes in the GnomAD database, including 28 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.015 ( 27 hom., cov: 32)

Exomes 𝑓: 0.014 ( 1 hom. )

Consequence

NPTN
ENST00000351217.10 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.822

Publications

2 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0146 (2229/152352) while in subpopulation EAS AF = 0.0542 (281/5184). AF 95% confidence interval is 0.049. There are 27 homozygotes in GnomAd4. There are 1107 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2229 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPTN	ENST00000351217.10	TSL:1	c.-463delT		5_prime_UTR	Exon 1 of 8	ENSP00000342958.6	Q9Y639-1
	NPTN	ENST00000970031.1		c.-463delT		upstream_gene	N/A	ENSP00000640090.1

Frequencies

GnomAD3 genomes

AF:

0.0146

AC:

2228

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0148

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.0541

Gnomad SAS

AF:

0.00703

Gnomad FIN

AF:

0.00357

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0148

Gnomad OTH

AF:

0.0143

GnomAD4 exome

AF:

0.0136

AC:

AN:

3826

Hom.:

Cov.:

AF XY:

0.0124

AC XY:

AN XY:

2174

show subpopulations

African (AFR)

AF:

0.0133

AC:

AN:

150

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00769

AC:

AN:

130

East Asian (EAS)

AF:

0.0588

AC:

AN:

136

South Asian (SAS)

AF:

0.00478

AC:

AN:

418

European-Finnish (FIN)

AF:

0.00

AC:

AN:

138

Middle Eastern (MID)

AF:

0.0385

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0135

AC:

AN:

2524

Other (OTH)

AF:

0.0161

AC:

AN:

248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0146

AC:

2229

AN:

152352

Hom.:

Cov.:

AF XY:

0.0149

AC XY:

1107

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.0148

AC:

616

AN:

41580

American (AMR)

AF:

0.0108

AC:

166

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0138

AC:

AN:

3472

East Asian (EAS)

AF:

0.0542

AC:

281

AN:

5184

South Asian (SAS)

AF:

0.00704

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00357

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0148

AC:

1009

AN:

68024

Other (OTH)

AF:

0.0142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

113

226

340

453

566

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.00171

Hom.:

Bravo

AF:

0.0152

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.82

Mutation Taster

=300/0

polymorphism

(source)

Splicing

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

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