rs79569204

Variant names:

• chr9-128618031-C-T
• rs79569204
• NM_001130438.3:c.5523C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-128618031-C-T
• chr9-128618031-C-A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001130438.3(SPTAN1):​c.5523C>T​(p.Ile1841Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00071 in 1,614,044 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00064 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00072 (18 hom.)
• Consequence: SPTAN1 NM_001130438.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.766
• Publications: 5 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 9-128618031-C-T is Benign according to our data. Variant chr9-128618031-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 139301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.766 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000637 (97/152250) while in subpopulation EAS AF = 0.0176 (91/5168). AF 95% confidence interval is 0.0147. There are 1 homozygotes in GnomAd4. There are 61 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 97 AD gene.

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.5523C>T	p.Ile1841Ile	synonymous	Exon 43 of 57	NP_001123910.1	Q13813-2
	SPTAN1	NM_001375318.1		c.5559C>T	p.Ile1853Ile	synonymous	Exon 44 of 59	NP_001362247.1
	SPTAN1	NM_001375310.1		c.5523C>T	p.Ile1841Ile	synonymous	Exon 43 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.5523C>T	p.Ile1841Ile	synonymous	Exon 43 of 57	ENSP00000361824.4	Q13813-2
	SPTAN1	ENST00000372731.8	TSL:1	c.5508C>T	p.Ile1836Ile	synonymous	Exon 42 of 56	ENSP00000361816.4	Q13813-1
	SPTAN1	ENST00000358161.9	TSL:1	c.5448C>T	p.Ile1816Ile	synonymous	Exon 41 of 55	ENSP00000350882.6	Q13813-3

Frequencies

GnomAD3 genomes AF: 0.000631 AC: 96 AN: 152130 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0174

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00166 AC: 417 AN: 251310 AF XY: 0.00150

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0216

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000718 AC: 1049 AN: 1461794 Hom.: 18 Cov.: 34 AF XY: 0.000670 AC XY: 487 AN XY: 727196

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0235 AC: 934 AN: 39700

South Asian (SAS) AF: 0.000684 AC: 59 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5754

European-Non Finnish (NFE) AF: 0.00000719 AC: 8 AN: 1111966

Other (OTH) AF: 0.000778 AC: 47 AN: 60380

GnomAD4 genome AF: 0.000637 AC: 97 AN: 152250 Hom.: 1 Cov.: 31 AF XY: 0.000819 AC XY: 61 AN XY: 74450

African (AFR) AF: 0.0000481 AC: 2 AN: 41544

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0176 AC: 91 AN: 5168

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

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

Alfa AF: 0.000128 Hom.: 0

Bravo AF: 0.000873

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Developmental and epileptic encephalopathy (1)
-	-	1	Developmental and epileptic encephalopathy, 5 (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	1.0
DANN	Benign	0.66
PhyloP100		-0.77
Mutation Taster		=94/6	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: rs79569204; hg19: chr9-131380310; COSMIC: COSV63985648;