chr9-128591558-G-C

Position:

• chr9-128591558-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001130438.3(SPTAN1):​c.3088G>C​(p.Ala1030Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SPTAN1 NM_001130438.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.79

Genes affected

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26160133).
• BP6: Variant 9-128591558-G-C is Benign according to our data. Variant chr9-128591558-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 530540.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTAN1	NM_001130438.3	c.3088G>C	p.Ala1030Pro	missense_variant	22/57	ENST00000372739.7	NP_001123910.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTAN1	ENST00000372739.7	c.3088G>C	p.Ala1030Pro	missense_variant	22/57	1	NM_001130438.3	ENSP00000361824.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Early infantile epileptic encephalopathy with suppression bursts Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 20, 2025

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;.;.;.;.
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D;D;D;D
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.26	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.86	L;.;L;L;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.3	N;.;N;N;.
REVEL	Benign	0.067
Sift	Benign	0.12	T;.;T;T;.
Sift4G	Benign	0.31	T;T;T;T;T
Polyphen		0.15	B;.;B;P;.
Vest4		0.59
MutPred		0.33		Gain of glycosylation at A1030 (P = 0.0262);Gain of glycosylation at A1030 (P = 0.0262);Gain of glycosylation at A1030 (P = 0.0262);Gain of glycosylation at A1030 (P = 0.0262);Gain of glycosylation at A1030 (P = 0.0262);
MVP		0.26
MPC		1.9
ClinPred		0.75	D
GERP RS		5.9
Varity_R		0.65
gMVP		0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs1554751018; hg19: chr9-131353837;