9-121283301-CTTTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTT

Variant names:

• chr9-121283301-C-CTTTT
• rs56834014
• NM_198252.3:c.-10+1751_-10+1754dupTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PVS1_Moderate

The NM_001353074.2(GSN):​c.-121-6_-121-3dupTTTT variant causes a splice acceptor, 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 0.000037 (0 hom., cov: 0)
• Consequence: GSN NM_001353074.2 splice_acceptor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.469
• Publications: 1 publications found

Genes affected

GSN (HGNC:4620): (gelsolin) The protein encoded by this gene binds to the "plus" ends of actin monomers and filaments to prevent monomer exchange. The encoded calcium-regulated protein functions in both assembly and disassembly of actin filaments. Defects in this gene are a cause of familial amyloidosis Finnish type (FAF). Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GSN-AS1 (HGNC:23372): (GSN antisense RNA 1)

ENSG00000239593 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.033198744 fraction of the gene. Cryptic splice site detected, with MaxEntScore 11, offset of 0 (no position change), new splice context is: ttttttttttttttttttAGacg. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353074.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSN	NM_198252.3	MANE Select	c.-10+1751_-10+1754dupTTTT		intron	N/A	NP_937895.1	P06396-2
	GSN	NM_001127663.2		c.99+763_99+766dupTTTT		intron	N/A	NP_001121135.2	A0A0A0MT01
	GSN	NM_001353076.2		c.-48+1751_-48+1754dupTTTT		intron	N/A	NP_001340005.1	A0A8V8TND7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSN	ENST00000432226.7	TSL:5 MANE Select	c.-10+1751_-10+1754dupTTTT		intron	N/A	ENSP00000404226.2	P06396-2
	GSN	ENST00000972594.1		c.-89_-86dupTTTT		5_prime_UTR	Exon 2 of 18	ENSP00000642653.1
	GSN	ENST00000900575.1		c.-10+1751_-10+1754dupTTTT		intron	N/A	ENSP00000570634.1

Frequencies

GnomAD3 genomes AF: 0.0000367 AC: 5 AN: 136070 Hom.: 0 Cov.: 0

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: 0.0000795

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000367 AC: 5 AN: 136070 Hom.: 0 Cov.: 0 AF XY: 0.0000460 AC XY: 3 AN XY: 65286

African (AFR) AF: 0.00 AC: 0 AN: 37280

American (AMR) AF: 0.00 AC: 0 AN: 13624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3302

East Asian (EAS) AF: 0.00 AC: 0 AN: 4702

South Asian (SAS) AF: 0.00 AC: 0 AN: 4164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000795 AC: 5 AN: 62928

Other (OTH) AF: 0.00 AC: 0 AN: 1840

Alfa AF: 0.00 Hom.: 340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.47

Splicing

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

Other links and lift over

dbSNP: rs56834014; hg19: chr9-124045579;