NM_017439.4:c.577-21_577-11dupTTTTTTTTTTT

Variant names:

• chr7-77377400-C-CAAAAAAAAAAA
• rs56314229
• NM_017439.4:c.577-21_577-11dupTTTTTTTTTTT

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 0 publications found

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

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSAP	NM_017439.4	c.577-21_577-11dupTTTTTTTTTTT		intron_variant	Intron 8 of 30	ENST00000257626.12	NP_059135.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSAP	ENST00000257626.12	c.577-11_577-10insTTTTTTTTTTT		intron_variant	Intron 8 of 30	1	NM_017439.4	ENSP00000257626.7
GSAP	ENST00000334003.11	n.468-11_468-10insTTTTTTTTTTT		intron_variant	Intron 7 of 18	2

Frequencies

GnomAD3 genomes AF: 0.000479 AC: 47 AN: 98042 Hom.: 0 Cov.: 0

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: 86 AN: 1086464 Hom.: 0 Cov.: 0 AF XY: 0.0000954 AC XY: 51 AN XY: 534566

African (AFR) AF: 0.000218 AC: 5 AN: 22962

American (AMR) AF: 0.000622 AC: 13 AN: 20908

Ashkenazi Jewish (ASJ) AF: 0.0000670 AC: 1 AN: 14920

East Asian (EAS) AF: 0.000957 AC: 23 AN: 24034

South Asian (SAS) AF: 0.000133 AC: 7 AN: 52472

European-Finnish (FIN) AF: 0.0000827 AC: 2 AN: 24172

Middle Eastern (MID) AF: 0.000327 AC: 1 AN: 3056

European-Non Finnish (NFE) AF: 0.0000386 AC: 34 AN: 881262

Other (OTH) AF: 0.00 AC: 0 AN: 42678

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000490 AC: 48 AN: 98046 Hom.: 0 Cov.: 0 AF XY: 0.000488 AC XY: 22 AN XY: 45110

African (AFR) AF: 0.00104 AC: 26 AN: 24932

American (AMR) AF: 0.000485 AC: 4 AN: 8252

Ashkenazi Jewish (ASJ) AF: 0.000375 AC: 1 AN: 2670

East Asian (EAS) AF: 0.00159 AC: 5 AN: 3140

South Asian (SAS) AF: 0.00 AC: 0 AN: 2936

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 166

European-Non Finnish (NFE) AF: 0.000215 AC: 11 AN: 51068

Other (OTH) AF: 0.000786 AC: 1 AN: 1272

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0

Splicing

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

Other links and lift over

dbSNP: rs56314229; hg19: chr7-77006717;