Genetic Variant GSAP:c.577-21_577-11dupTTTTTTTTTTT (chr7-77377400-C-CAAAAAAAAAAA) – 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.577-21_577-11dupTTTTTTTTTTT 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 0.00049 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000079 ( 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:

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.577-21_577-11dupTTTTTTTTTTT	intron	N/A	NP_059135.2	A4D1B5-1
GSAP	NM_001350896.2		c.577-21_577-11dupTTTTTTTTTTT	intron	N/A	NP_001337825.1
GSAP	NM_001350897.2		c.577-21_577-11dupTTTTTTTTTTT	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_577-10insTTTTTTTTTTT	intron	N/A	ENSP00000257626.7	A4D1B5-1
GSAP	ENST00000943097.1		c.577-11_577-10insTTTTTTTTTTT	intron	N/A	ENSP00000613156.1
GSAP	ENST00000880888.1		c.577-11_577-10insTTTTTTTTTTT	intron	N/A	ENSP00000550947.1

Frequencies

GnomAD3 genomes

AF:

0.000479

AC:

AN:

98042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000364

Gnomad ASJ

AF:

0.000375

Gnomad EAS

AF:

0.00159

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000215

Gnomad OTH

AF:

0.000786

GnomAD4 exome

AF:

0.0000792

AC:

AN:

1086464

Hom.:

Cov.:

AF XY:

0.0000954

AC XY:

AN XY:

534566

show subpopulations

African (AFR)

AF:

0.000218

AC:

AN:

22962

American (AMR)

AF:

0.000622

AC:

AN:

20908

Ashkenazi Jewish (ASJ)

AF:

0.0000670

AC:

AN:

14920

East Asian (EAS)

AF:

0.000957

AC:

AN:

24034

South Asian (SAS)

AF:

0.000133

AC:

AN:

52472

European-Finnish (FIN)

AF:

0.0000827

AC:

AN:

24172

Middle Eastern (MID)

AF:

0.000327

AC:

AN:

3056

European-Non Finnish (NFE)

AF:

0.0000386

AC:

AN:

881262

Other (OTH)

AF:

0.00

AC:

AN:

42678

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

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: AS_VQSR

AF:

0.000490

AC:

AN:

98046

Hom.:

Cov.:

AF XY:

0.000488

AC XY:

AN XY:

45110

show subpopulations

African (AFR)

AF:

0.00104

AC:

AN:

24932

American (AMR)

AF:

0.000485

AC:

AN:

8252

Ashkenazi Jewish (ASJ)

AF:

0.000375

AC:

AN:

2670

East Asian (EAS)

AF:

0.00159

AC:

AN:

3140

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:

0.000215

AC:

AN:

51068

Other (OTH)

AF:

0.000786

AC:

AN:

1272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

7-77377400-CAAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAAAAAA

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