Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM2PP3_ModerateBP6_Moderate
The NM_001130438.3(SPTAN1):c.2201T>C(p.Ile734Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
SPTAN1 (HGNC:11273): (spectrin alpha, non-erythrocytic 1) Spectrins are a family of filamentous cytoskeletal proteins that function as essential scaffold proteins that stabilize the plasma membrane and organize intracellular organelles. Spectrins are composed of alpha and beta dimers that associate to form tetramers linked in a head-to-head arrangement. This gene encodes an alpha spectrin that is specifically expressed in nonerythrocytic cells. The encoded protein has been implicated in other cellular functions including DNA repair and cell cycle regulation. Mutations in this gene are the cause of early infantile epileptic encephalopathy-5. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Sep 2010]
SPTAN1 Gene-Disease associations (from GenCC):
developmental and epileptic encephalopathy, 5
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
infantile spasms
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.869
BP6
Variant 9-128584289-T-C is Benign according to our data. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars.