7-77377400-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAAAA

Position:

• chr7-77377400-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_017439.4(GSAP):​c.577-11_577-10insTTTTTTTTTT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00054 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: GSAP NM_017439.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSAP	NM_017439.4	c.577-11_577-10insTTTTTTTTTT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000257626.12	NP_059135.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSAP	ENST00000257626.12	c.577-11_577-10insTTTTTTTTTT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_017439.4	ENSP00000257626	P1
GSAP	ENST00000334003.11	n.468-11_468-10insTTTTTTTTTT		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.000541 AC: 53 AN: 98044 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000924

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000484

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00254

Gnomad SAS AF: 0.000339

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00568

Gnomad NFE AF: 0.000313

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000100 AC: 109 AN: 1086460 Hom.: 0 Cov.: 0 AF XY: 0.000108 AC XY: 58 AN XY: 534564

Gnomad4 AFR exome AF: 0.000392

Gnomad4 AMR exome AF: 0.000430

Gnomad4 ASJ exome AF: 0.000268

Gnomad4 EAS exome AF: 0.00112

Gnomad4 SAS exome AF: 0.000362

Gnomad4 FIN exome AF: 0.0000414

Gnomad4 NFE exome AF: 0.0000409

Gnomad4 OTH exome AF: 0.0000937

GnomAD4 genome AF: 0.000541 AC: 53 AN: 98048 Hom.: 0 Cov.: 0 AF XY: 0.000510 AC XY: 23 AN XY: 45120

Gnomad4 AFR AF: 0.000923

Gnomad4 AMR AF: 0.000484

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00255

Gnomad4 SAS AF: 0.000341

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000313

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs56314229; hg19: chr7-77006717;