rs56314229

chr7-77377400-CAAAAAAAAAAAA-Cchr7-77377400-CAAAAAAAAAAAA-CAAAchr7-77377400-CAAAAAAAAAAAA-CAAAAchr7-77377400-CAAAAAAAAAAAA-CAAAAAchr7-77377400-CAAAAAAAAAAAA-CAAAAAAchr7-77377400-CAAAAAAAAAAAA-CAAAAAAAchr7-77377400-CAAAAAAAAAAAA-CAAAAAAAAchr7-77377400-CAAAAAAAAAAAA-CAAAAAAAAAchr7-77377400-CAAAAAAAAAAAA-CAAAAAAAAAAchr7-77377400-CAAAAAAAAAAAA-CAAAAAAAAAAAchr7-77377400-CAAAAAAAAAAAA-CAAAAAAAAAAAAAchr7-77377400-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAchr7-77377400-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAchr7-77377400-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAchr7-77377400-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAchr7-77377400-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAchr7-77377400-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAchr7-77377400-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAAchr7-77377400-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAAAchr7-77377400-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAAAAchr7-77377400-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAAAAAchr7-77377400-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAAAAAAchr7-77377400-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017439.4(GSAP):c.577-22_577-11del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000092 in 1,086,468 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 9.2e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GSAP NM_017439.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSAP	NM_017439.4	c.577-22_577-11del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000257626.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSAP	ENST00000257626.12	c.577-22_577-11del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_017439.4	P1
GSAP	ENST00000334003.11	n.468-22_468-11del		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 98072 Hom.: 0 Cov.: 0 FAILED QC

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: 9.20e-7 AC: 1 AN: 1086468 Hom.: 0 AF XY: 0.00000187 AC XY: 1 AN XY: 534570

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000113

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 98072 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 45110

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

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;