Genetic Variant GSAP:c.577-23_577-11dupTTTTTTTTTTTTT (chr7-77377400-C-CAAAAAAAAAAAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_017439.4(GSAP):c.577-23_577-11dupTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GSAP
NM_017439.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

Publications

0 publications found

Variant links:

Genes affected

GSAP (HGNC:28042): (gamma-secretase activating protein) Accumulation of neurotoxic amyloid-beta is a major hallmark of Alzheimer disease (AD; MIM 104300). Formation of amyloid-beta is catalyzed by gamma-secretase (see PSEN1; MIM 104311), a protease with numerous substrates. PION, or GSAP, selectively increases amyloid-beta production through a mechanism involving its interaction with both gamma-secretase and its substrate, the amyloid-beta precursor protein (APP; MIM 104760) C-terminal fragment (APP-CTF) (He et al., 2010 [PubMed 20811458]).[supplied by OMIM, Nov 2010]

GSAP links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017439.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GSAP	NM_017439.4	MANE Select	c.577-23_577-11dupTTTTTTTTTTTTT	intron	N/A	NP_059135.2	A4D1B5-1
GSAP	NM_001350896.2		c.577-23_577-11dupTTTTTTTTTTTTT	intron	N/A	NP_001337825.1
GSAP	NM_001350897.2		c.577-23_577-11dupTTTTTTTTTTTTT	intron	N/A	NP_001337826.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GSAP	ENST00000257626.12	TSL:1 MANE Select	c.577-11_577-10insTTTTTTTTTTTTT	intron	N/A	ENSP00000257626.7	A4D1B5-1
GSAP	ENST00000943097.1		c.577-11_577-10insTTTTTTTTTTTTT	intron	N/A	ENSP00000613156.1
GSAP	ENST00000880888.1		c.577-11_577-10insTTTTTTTTTTTTT	intron	N/A	ENSP00000550947.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

98070

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1086470

Hom.:

Cov.:

AF XY:

0.0000224

AC XY:

AN XY:

534570

show subpopulations

African (AFR)

AF:

0.0000436

AC:

AN:

22962

American (AMR)

AF:

0.000191

AC:

AN:

20908

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14920

East Asian (EAS)

AF:

0.000291

AC:

AN:

24036

South Asian (SAS)

AF:

0.0000191

AC:

AN:

52472

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24172

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3056

European-Non Finnish (NFE)

AF:

0.00000908

AC:

AN:

881266

Other (OTH)

AF:

0.0000469

AC:

AN:

42678

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

98070

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

45108

African (AFR)

AF:

0.00

AC:

AN:

24900

American (AMR)

AF:

0.00

AC:

AN:

8258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2670

East Asian (EAS)

AF:

0.00

AC:

AN:

3160

South Asian (SAS)

AF:

0.00

AC:

AN:

2948

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2950

Middle Eastern (MID)

AF:

0.00

AC:

AN:

176

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

51076

Other (OTH)

AF:

0.00

AC:

AN:

1272

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over