Variant rs3817622 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_172341.4(PSENEN):c.62-93T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0974 in 1,125,906 control chromosomes in the GnomAD database, including 5,964 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 0.099 ( 843 hom., cov: 32)

Exomes 𝑓: 0.097 ( 5121 hom. )

Consequence

PSENEN
NM_172341.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.598

Variant links:

Genes affected

PSENEN (HGNC:30100): (presenilin enhancer, gamma-secretase subunit) Presenilins, which are components of the gamma-secretase protein complex, are required for intramembranous processing of some type I transmembrane proteins, such as the Notch proteins and the beta-amyloid precursor protein. Signaling by Notch receptors mediates a wide range of developmental cell fates. Processing of the beta-amyloid precursor protein generates neurotoxic amyloid beta peptides, the major component of senile plaques associated with Alzheimer's disease. This gene encodes a protein that is required for Notch pathway signaling, and for the activity and accumulation of gamma-secretase. Mutations resulting in haploinsufficiency for this gene cause familial acne inversa-2 (ACNINV2). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

PSENEN links:

ENSG00000188223 (HGNC:):

ENSG00000188223 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0995 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSENEN	NM_172341.4 linkuse as main transcript	c.62-93T>A		intron_variant		ENST00000587708.7	NP_758844.1	Q9NZ42
PSENEN	NM_001281532.3 linkuse as main transcript	c.62-93T>A		intron_variant			NP_001268461.1	Q9NZ42

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
PSENEN	ENST00000587708.7 linkuse as main transcript	c.62-93T>A	intron_variant	1	NM_172341.4	ENSP00000468411.1	Q9NZ42
PSENEN	ENST00000222266.2 linkuse as main transcript	c.62-93T>A	intron_variant	1		ENSP00000222266.1	Q9NZ42
ENSG00000188223	ENST00000591613.2 linkuse as main transcript	n.62-93T>A	intron_variant	2		ENSP00000468389.2	K7ERS5
PSENEN	ENST00000591949.1 linkuse as main transcript	c.62-93T>A	intron_variant	2		ENSP00000468593.1	K7ES79

Frequencies

GnomAD3 genomes

AF:

0.0993

AC:

15084

AN:

151928

Hom.:

842

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0831

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.0895

Gnomad ASJ

AF:

0.0685

Gnomad EAS

AF:

0.0879

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.184

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0998

Gnomad OTH

AF:

0.0798

GnomAD4 exome

AF:

0.0971

AC:

94572

AN:

973860

Hom.:

5121

AF XY:

0.0983

AC XY:

49469

AN XY:

503468

show subpopulations

Gnomad4 AFR exome

AF:

0.0866

Gnomad4 AMR exome

AF:

0.106

Gnomad4 ASJ exome

AF:

0.0620

Gnomad4 EAS exome

AF:

0.0810

Gnomad4 SAS exome

AF:

0.111

Gnomad4 FIN exome

AF:

0.185

Gnomad4 NFE exome

AF:

0.0933

Gnomad4 OTH exome

AF:

0.0875

GnomAD4 genome

AF:

0.0994

AC:

15106

AN:

152046

Hom.:

843

Cov.:

AF XY:

0.104

AC XY:

7728

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0831

Gnomad4 AMR

AF:

0.0901

Gnomad4 ASJ

AF:

0.0685

Gnomad4 EAS

AF:

0.0883

Gnomad4 SAS

AF:

0.107

Gnomad4 FIN

AF:

0.184

Gnomad4 NFE

AF:

0.0998

Gnomad4 OTH

AF:

0.0799

Alfa

AF:

0.110

Hom.:

128

Bravo

AF:

0.0896

Asia WGS

AF:

0.100

AC:

346

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.83

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over