1-158611166-C-CACACAT

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_003126.4(SPTA1):​c.*97_*98insATGTGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000389 in 1,387,628 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0021 ( 2 hom., cov: 28)
Exomes 𝑓: 0.00019 ( 2 hom. )

Consequence

SPTA1
NM_003126.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4

Conservation

PhyloP100: 1.26
Variant links:
Genes affected
OR10Z1 (HGNC:14996): (olfactory receptor family 10 subfamily Z member 1) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]
SPTA1 (HGNC:11272): (spectrin alpha, erythrocytic 1) This gene encodes a member of a family of molecular scaffold proteins that link the plasma membrane to the actin cytoskeleton and functions in the determination of cell shape, arrangement of transmembrane proteins, and organization of organelles. The encoded protein is primarily composed of 22 spectrin repeats which are involved in dimer formation. It forms a component of the erythrocyte plasma membrane. Mutations in this gene result in a variety of hereditary red blood cell disorders, including elliptocytosis-2, pyropoikilocytosis, and spherocytosis, type 3. [provided by RefSeq, Aug 2017]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BS2
High Homozygotes in GnomAd4 at 2 AD,AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OR10Z1NM_001004478.2 linkuse as main transcriptc.*3786_*3787insACACAT 3_prime_UTR_variant 2/2 ENST00000641002.1
SPTA1NM_003126.4 linkuse as main transcriptc.*97_*98insATGTGT 3_prime_UTR_variant 52/52 ENST00000643759.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OR10Z1ENST00000641002.1 linkuse as main transcriptc.*3786_*3787insACACAT 3_prime_UTR_variant 2/2 NM_001004478.2 P1
SPTA1ENST00000643759.2 linkuse as main transcriptc.*97_*98insATGTGT 3_prime_UTR_variant 52/52 NM_003126.4 P1P02549-1
SPTA1ENST00000485680.1 linkuse as main transcript downstream_gene_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00208
AC:
307
AN:
147330
Hom.:
2
Cov.:
28
show subpopulations
Gnomad AFR
AF:
0.00729
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000345
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000101
Gnomad MID
AF:
0.00323
Gnomad NFE
AF:
0.0000751
Gnomad OTH
AF:
0.000498
GnomAD4 exome
AF:
0.000185
AC:
230
AN:
1240194
Hom.:
2
Cov.:
17
AF XY:
0.000153
AC XY:
96
AN XY:
625760
show subpopulations
Gnomad4 AFR exome
AF:
0.00465
Gnomad4 AMR exome
AF:
0.000494
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000500
Gnomad4 FIN exome
AF:
0.000103
Gnomad4 NFE exome
AF:
0.0000325
Gnomad4 OTH exome
AF:
0.000461
GnomAD4 genome
AF:
0.00210
AC:
310
AN:
147434
Hom.:
2
Cov.:
28
AF XY:
0.00187
AC XY:
134
AN XY:
71714
show subpopulations
Gnomad4 AFR
AF:
0.00735
Gnomad4 AMR
AF:
0.000344
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000101
Gnomad4 NFE
AF:
0.0000751
Gnomad4 OTH
AF:
0.000492

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Elliptocytosis Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
not provided Uncertain:1
Uncertain significance, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Pyropoikilocytosis, hereditary Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Spherocytosis, Recessive Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1553221961; hg19: chr1-158580956; API