9-121282470-C-T

Variant names:

• chr9-121282470-C-T
• rs145775883
• NM_198252.3:c.-10+908C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001127663.2(GSN):​c.19C>T​(p.Arg7Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000356 in 1,267,542 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00038 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00035 (2 hom.)
• Consequence: GSN NM_001127663.2 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0570
• Publications: 0 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.040370256).
• BP6: Variant 9-121282470-C-T is Benign according to our data. Variant chr9-121282470-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3058775.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127663.2. 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+908C>T		intron	N/A	NP_937895.1	P06396-2
	GSN	NM_001127663.2		c.19C>T	p.Arg7Cys	missense	Exon 3 of 19	NP_001121135.2	A0A0A0MT01
	GSN	NM_001353068.2		c.-119C>T		5_prime_UTR	Exon 3 of 20	NP_001339997.1	P06396-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSN	ENST00000432226.7	TSL:5 MANE Select	c.-10+908C>T		intron	N/A	ENSP00000404226.2	P06396-2
	GSN	ENST00000449733.7	TSL:2	c.19C>T	p.Arg7Cys	missense	Exon 3 of 19	ENSP00000409358.2	A0A0A0MT01
	GSN	ENST00000900518.1		c.-315C>T		5_prime_UTR	Exon 10 of 27	ENSP00000570577.1

Frequencies

GnomAD3 genomes AF: 0.000381 AC: 58 AN: 152198 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000352 AC: 393 AN: 1115226 Hom.: 2 Cov.: 28 AF XY: 0.000349 AC XY: 184 AN XY: 527884

African (AFR) AF: 0.000128 AC: 3 AN: 23478

American (AMR) AF: 0.00 AC: 0 AN: 11640

Ashkenazi Jewish (ASJ) AF: 0.000815 AC: 12 AN: 14716

East Asian (EAS) AF: 0.00 AC: 0 AN: 28150

South Asian (SAS) AF: 0.00114 AC: 26 AN: 22778

European-Finnish (FIN) AF: 0.00213 AC: 77 AN: 36124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2964

European-Non Finnish (NFE) AF: 0.000272 AC: 253 AN: 930710

Other (OTH) AF: 0.000493 AC: 22 AN: 44666

GnomAD4 genome AF: 0.000381 AC: 58 AN: 152316 Hom.: 1 Cov.: 33 AF XY: 0.000349 AC XY: 26 AN XY: 74470

African (AFR) AF: 0.000120 AC: 5 AN: 41570

American (AMR) AF: 0.000131 AC: 2 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00141 AC: 15 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000454 Hom.: 0

Bravo AF: 0.000204

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00 AC: 0

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	GSN-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.9
DANN	Benign	0.70
DEOGEN2	Benign	0.0061	T
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.040	T
PhyloP100		-0.057
Vest4		0.041
MVP		0.67
GERP RS		0.96
Mutation Taster		=300/0	polymorphism

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

Other links and lift over

dbSNP: rs145775883; hg19: chr9-124044748;