Genetic Variant ENST00000351217.10:c.-226T>A (chr15-73633441-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000351217.10(NPTN):c.-226T>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 0.00000407 in 245,806 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPTN	NM_012428.4 link	c.-226T>A		upstream_gene_variant		ENST00000345330.9	NP_036560.1	Q9Y639-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPTN	ENST00000345330.9 link	c.-226T>A		upstream_gene_variant		1	NM_012428.4	ENSP00000290401.4		Q9Y639-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000407

AC:

AN:

245806

Hom.:

Cov.:

AF XY:

0.00000788

AC XY:

AN XY:

126866

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

6666

American (AMR)

AF:

0.00

AC:

AN:

6836

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8864

East Asian (EAS)

AF:

0.00

AC:

AN:

21688

South Asian (SAS)

AF:

0.00

AC:

AN:

8688

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20634

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1222

European-Non Finnish (NFE)

AF:

0.00000643

AC:

AN:

155402

Other (OTH)

AF:

0.00

AC:

AN:

15806

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

912

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

-0.50

PromoterAI

-0.42

Neutral

(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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over