rs34084388

Variant names:

• chr9-128584431-C-A
• rs34084388
• NM_001130438.3:c.2343C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-128584431-C-A
• chr9-128584431-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001130438.3(SPTAN1):​c.2343C>A​(p.Ala781Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00561 in 1,614,036 control chromosomes in the GnomAD database, including 392 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A781A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.029 (197 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (195 hom.)
• Consequence: SPTAN1 NM_001130438.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -4.01
• Publications: 2 publications found

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]

SPTAN1 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 5

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P, Ambry Genetics
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• neuronopathy, distal hereditary motor, autosomal dominant 11

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• spastic paraplegia 91, autosomal dominant, with or without cerebellar ataxia

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• infantile spasms

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary spastic paraplegia

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 9-128584431-C-A is Benign according to our data. Variant chr9-128584431-C-A is described in ClinVar as Benign. ClinVar VariationId is 139277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.01 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0983 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130438.3. 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
	SPTAN1	NM_001130438.3	MANE Select	c.2343C>A	p.Ala781Ala	synonymous	Exon 17 of 57	NP_001123910.1	Q13813-2
	SPTAN1	NM_001375318.1		c.2379C>A	p.Ala793Ala	synonymous	Exon 18 of 59	NP_001362247.1
	SPTAN1	NM_001375310.1		c.2343C>A	p.Ala781Ala	synonymous	Exon 17 of 58	NP_001362239.1	A0A994J6W3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTAN1	ENST00000372739.7	TSL:1 MANE Select	c.2343C>A	p.Ala781Ala	synonymous	Exon 17 of 57	ENSP00000361824.4	Q13813-2
	SPTAN1	ENST00000372731.8	TSL:1	c.2343C>A	p.Ala781Ala	synonymous	Exon 17 of 56	ENSP00000361816.4	Q13813-1
	SPTAN1	ENST00000358161.9	TSL:1	c.2343C>A	p.Ala781Ala	synonymous	Exon 17 of 55	ENSP00000350882.6	Q13813-3

Frequencies

GnomAD3 genomes AF: 0.0289 AC: 4401 AN: 152054 Hom.: 195 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0100

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.0177

GnomAD2 exomes AF: 0.00756 AC: 1897 AN: 250904 AF XY: 0.00563

Gnomad AFR exome AF: 0.103

Gnomad AMR exome AF: 0.00440

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000406

Gnomad OTH exome AF: 0.00506

GnomAD4 exome AF: 0.00317 AC: 4631 AN: 1461864 Hom.: 195 Cov.: 37 AF XY: 0.00273 AC XY: 1986 AN XY: 727238

African (AFR) AF: 0.106 AC: 3557 AN: 33478

American (AMR) AF: 0.00499 AC: 223 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000313 AC: 27 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00885 AC: 51 AN: 5764

European-Non Finnish (NFE) AF: 0.000319 AC: 355 AN: 1112006

Other (OTH) AF: 0.00690 AC: 417 AN: 60396

GnomAD4 genome AF: 0.0291 AC: 4424 AN: 152172 Hom.: 197 Cov.: 32 AF XY: 0.0288 AC XY: 2144 AN XY: 74384

African (AFR) AF: 0.101 AC: 4186 AN: 41500

American (AMR) AF: 0.0100 AC: 153 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000632 AC: 43 AN: 68002

Other (OTH) AF: 0.0175 AC: 37 AN: 2114

Alfa AF: 0.0105 Hom.: 31

Bravo AF: 0.0337

Asia WGS AF: 0.0110 AC: 37 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000830

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	Developmental and epileptic encephalopathy (1)
-	-	1	Developmental and epileptic encephalopathy, 5 (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.39
DANN	Benign	0.68
PhyloP100		-4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=81/19	polymorphism (auto)

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: rs34084388; hg19: chr9-131346710;