chr12-108788995-G-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_018984.4(SSH1):c.2143C>G(p.Leu715Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00449 in 1,609,696 control chromosomes in the GnomAD database, including 302 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.025 ( 171 hom., cov: 32)
Exomes 𝑓: 0.0024 ( 131 hom. )
Consequence
SSH1
NM_018984.4 missense
NM_018984.4 missense
Scores
3
15
Clinical Significance
Conservation
PhyloP100: 2.27
Genes affected
SSH1 (HGNC:30579): (slingshot protein phosphatase 1) The protein encoded by this gene belongs to the slingshot homolog (SSH) family of phosphatases, which regulate actin filament dynamics. The SSH proteins dephosphorylate and activate the actin binding/depolymerizing factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly. Cofilin is inactivated by kinases such as LIM domain kinase-1 (LIMK1), which may also be dephosphorylated and inactivated by SSH proteins. The SSH family thus appears to play a role in actin dynamics by reactivating cofilin proteins. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0020462275).
BP6
?
Variant 12-108788995-G-C is Benign according to our data. Variant chr12-108788995-G-C is described in ClinVar as [Benign]. Clinvar id is 776749.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0846 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SSH1 | NM_018984.4 | c.2143C>G | p.Leu715Val | missense_variant | 15/15 | ENST00000326495.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SSH1 | ENST00000326495.10 | c.2143C>G | p.Leu715Val | missense_variant | 15/15 | 1 | NM_018984.4 | P2 | |
SSH1 | ENST00000546433.5 | c.*1136C>G | 3_prime_UTR_variant, NMD_transcript_variant | 7/7 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0248 AC: 3771AN: 152140Hom.: 171 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.00612 AC: 1526AN: 249484Hom.: 61 AF XY: 0.00439 AC XY: 592AN XY: 134934
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GnomAD4 exome AF: 0.00238 AC: 3465AN: 1457438Hom.: 131 Cov.: 33 AF XY: 0.00204 AC XY: 1477AN XY: 724414
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GnomAD4 genome ? AF: 0.0248 AC: 3769AN: 152258Hom.: 171 Cov.: 32 AF XY: 0.0233 AC XY: 1737AN XY: 74452
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365
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?
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930
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
P;P
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at