NM_198252.3:c.-10+1754dupT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_198252.3(GSN):​c.-10+1754dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 0)
Exomes 𝑓: 0.0032 ( 0 hom. )

Consequence

GSN
NM_198252.3 intron

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.469
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd4 at 165 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GSNNM_198252.3 linkc.-10+1754dupT intron_variant Intron 2 of 17 ENST00000432226.7 NP_937895.1 P06396-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GSNENST00000432226.7 linkc.-10+1754dupT intron_variant Intron 2 of 17 5 NM_198252.3 ENSP00000404226.2 P06396-2Q5T0I0

Frequencies

GnomAD3 genomes
AF:
0.00121
AC:
165
AN:
136052
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.00182
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000220
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000213
Gnomad SAS
AF:
0.000240
Gnomad FIN
AF:
0.00127
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00129
Gnomad OTH
AF:
0.00109
GnomAD4 exome
AF:
0.00318
AC:
15
AN:
4716
Hom.:
0
Cov.:
0
AF XY:
0.00311
AC XY:
7
AN XY:
2248
show subpopulations
Gnomad4 AMR exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00303
Gnomad4 NFE exome
AF:
0.0200
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00121
AC:
165
AN:
136054
Hom.:
0
Cov.:
0
AF XY:
0.000919
AC XY:
60
AN XY:
65306
show subpopulations
Gnomad4 AFR
AF:
0.00182
Gnomad4 AMR
AF:
0.000220
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000213
Gnomad4 SAS
AF:
0.000242
Gnomad4 FIN
AF:
0.00127
Gnomad4 NFE
AF:
0.00129
Gnomad4 OTH
AF:
0.00108

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Finnish type amyloidosis Uncertain:1
May 05, 2022
Department of Pathology and Laboratory Medicine, Sinai Health System
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs56834014; hg19: chr9-124045579; API