Genetic Variant GSN:c.-10+1753_-10+1754delTT (chr9-121283301-CTT-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001353074.2(GSN):c.-121-4_-121-3delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.004 in 140,638 control chromosomes in the GnomAD database, including 1 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00084 ( 0 hom., cov: 0)

Exomes 𝑓: 0.097 ( 1 hom. )

Consequence

GSN
NM_001353074.2 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.469

Publications

1 publications found

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

GSN-AS1 links:

ENSG00000239593 (HGNC:):

ENSG00000239593 links:

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new If you want to explore the variant's impact on the transcript NM_001353074.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GSN	NM_198252.3	MANE Select	c.-10+1753_-10+1754delTT	intron	N/A	NP_937895.1	P06396-2
GSN	NM_001127663.2		c.99+765_99+766delTT	intron	N/A	NP_001121135.2	A0A0A0MT01
GSN	NM_001353076.2		c.-48+1753_-48+1754delTT	intron	N/A	NP_001340005.1	A0A8V8TND7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GSN	ENST00000432226.7	TSL:5 MANE Select	c.-10+1753_-10+1754delTT	intron	N/A	ENSP00000404226.2	P06396-2
GSN	ENST00000972594.1		c.-87_-86delTT	5_prime_UTR	Exon 2 of 18	ENSP00000642653.1
GSN	ENST00000900575.1		c.-10+1753_-10+1754delTT	intron	N/A	ENSP00000570634.1

Frequencies

GnomAD3 genomes

AF:

0.000838

AC:

114

AN:

136022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000134

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000587

Gnomad ASJ

AF:

0.000303

Gnomad EAS

AF:

0.000851

Gnomad SAS

AF:

0.000240

Gnomad FIN

AF:

0.00409

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00105

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0973

AC:

449

AN:

4614

Hom.:

AF XY:

0.0966

AC XY:

212

AN XY:

2194

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.333

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0966

AC:

437

AN:

4526

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.120

AC:

AN:

Other (OTH)

AF:

0.133

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.314

Heterozygous variant carriers

131

164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000838

AC:

114

AN:

136024

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

65282

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000134

AC:

AN:

37318

American (AMR)

AF:

0.000587

AC:

AN:

13636

Ashkenazi Jewish (ASJ)

AF:

0.000303

AC:

AN:

3302

East Asian (EAS)

AF:

0.000854

AC:

AN:

4686

South Asian (SAS)

AF:

0.000242

AC:

AN:

4140

European-Finnish (FIN)

AF:

0.00409

AC:

AN:

7090

Middle Eastern (MID)

AF:

0.00

AC:

AN:

270

European-Non Finnish (NFE)

AF:

0.00105

AC:

AN:

62894

Other (OTH)

AF:

0.00

AC:

AN:

1848

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.333

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Mutation Taster

=100/0

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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9-121283301-CTTTTTTTTTTTTTT-CTTTTTTTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over