Variant 9-121286183-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001258029.2(GSN):c.40T>C(p.Trp14Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 1,529,228 control chromosomes in the GnomAD database, including 2,598 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/11 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 624 hom., cov: 32)

Exomes 𝑓: 0.025 ( 1974 hom. )

Consequence

GSN
NM_001258029.2 missense, splice_region

Scores

Splicing: ADA: 0.00002783

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.887

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 links:

GSN (HGNC:):

GSN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016709864).

BP6

Variant 9-121286183-T-C is Benign according to our data. Variant chr9-121286183-T-C is described in ClinVar as [Benign]. Clinvar id is 1267128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSN	NM_198252.3 linkuse as main transcript	c.-10+4621T>C		intron_variant		ENST00000432226.7	NP_937895.1	P06396-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSN	ENST00000432226.7 linkuse as main transcript	c.-10+4621T>C		intron_variant		5	NM_198252.3	ENSP00000404226.2		P06396-2Q5T0I0

Frequencies

GnomAD3 genomes

AF:

0.0630

AC:

9574

AN:

152072

Hom.:

622

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.145

Gnomad ASJ

AF:

0.00952

Gnomad EAS

AF:

0.134

Gnomad SAS

AF:

0.0848

Gnomad FIN

AF:

0.0277

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0104

Gnomad OTH

AF:

0.0502

GnomAD3 exomes

AF:

0.0809

AC:

10358

AN:

128050

Hom.:

922

AF XY:

0.0704

AC XY:

4939

AN XY:

70128

show subpopulations

Gnomad AFR exome

AF:

0.128

Gnomad AMR exome

AF:

0.228

Gnomad ASJ exome

AF:

0.0118

Gnomad EAS exome

AF:

0.148

Gnomad SAS exome

AF:

0.0722

Gnomad FIN exome

AF:

0.0269

Gnomad NFE exome

AF:

0.00956

Gnomad OTH exome

AF:

0.0476

GnomAD4 exome

AF:

0.0254

AC:

35006

AN:

1377038

Hom.:

1974

Cov.:

AF XY:

0.0260

AC XY:

17682

AN XY:

679928

show subpopulations

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.216

Gnomad4 ASJ exome

AF:

0.0129

Gnomad4 EAS exome

AF:

0.142

Gnomad4 SAS exome

AF:

0.0733

Gnomad4 FIN exome

AF:

0.0305

Gnomad4 NFE exome

AF:

0.00829

Gnomad4 OTH exome

AF:

0.0360

GnomAD4 genome

AF:

0.0630

AC:

9589

AN:

152190

Hom.:

624

Cov.:

AF XY:

0.0663

AC XY:

4935

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.123

Gnomad4 AMR

AF:

0.145

Gnomad4 ASJ

AF:

0.00952

Gnomad4 EAS

AF:

0.134

Gnomad4 SAS

AF:

0.0851

Gnomad4 FIN

AF:

0.0277

Gnomad4 NFE

AF:

0.0105

Gnomad4 OTH

AF:

0.0497

Alfa

AF:

0.0287

Hom.:

Bravo

AF:

0.0774

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00804

AC:

ExAC

AF:

0.0361

AC:

637

Asia WGS

AF:

0.102

AC:

353

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.48

DEOGEN2

Benign

0.0089

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.13

MetaRNN

Benign

0.0017

Sift4G

Benign

0.83

Vest4

0.13

GERP RS

-0.43

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000028

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.080

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over