Genetic Variant GSAP:c.577-22_577-11dupTTTTTTTTTTTT (chr7-77377400-C-CAAAAAAAAAAAA) – 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.577-22_577-11dupTTTTTTTTTTTT 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 0.00012 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000024 ( 0 hom. )

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:

Genome browser will be placed here

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.577-22_577-11dupTTTTTTTTTTTT	intron	N/A	NP_059135.2	A4D1B5-1
GSAP	NM_001350896.2		c.577-22_577-11dupTTTTTTTTTTTT	intron	N/A	NP_001337825.1
GSAP	NM_001350897.2		c.577-22_577-11dupTTTTTTTTTTTT	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_577-10insTTTTTTTTTTTT	intron	N/A	ENSP00000257626.7	A4D1B5-1
GSAP	ENST00000943097.1		c.577-11_577-10insTTTTTTTTTTTT	intron	N/A	ENSP00000613156.1
GSAP	ENST00000880888.1		c.577-11_577-10insTTTTTTTTTTTT	intron	N/A	ENSP00000550947.1

Frequencies

GnomAD3 genomes

AF:

0.000122

AC:

AN:

98070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000281

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000121

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000316

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000587

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000239

AC:

AN:

1086466

Hom.:

Cov.:

AF XY:

0.0000262

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:

0.0000670

AC:

AN:

14920

East Asian (EAS)

AF:

0.000291

AC:

AN:

24034

South Asian (SAS)

AF:

0.0000572

AC:

AN:

52472

European-Finnish (FIN)

AF:

0.0000414

AC:

AN:

24172

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3056

European-Non Finnish (NFE)

AF:

0.00000567

AC:

AN:

881264

Other (OTH)

AF:

0.0000937

AC:

AN:

42678

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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

AF:

0.000122

AC:

AN:

98074

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

AN XY:

45128

show subpopulations

African (AFR)

AF:

0.000281

AC:

AN:

24942

American (AMR)

AF:

0.000121

AC:

AN:

8256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2670

East Asian (EAS)

AF:

0.000317

AC:

AN:

3150

South Asian (SAS)

AF:

0.00

AC:

AN:

2936

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2950

Middle Eastern (MID)

AF:

0.00

AC:

AN:

166

European-Non Finnish (NFE)

AF:

0.0000587

AC:

AN:

51072

Other (OTH)

AF:

0.00

AC:

AN:

1272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

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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7-77377400-CAAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAAAAAAA

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