Variant chr1-158611166-C-CACACAT details in Genebe, Genetics Data Aggregator

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]

OR10Z1 links:

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]

SPTA1 links:

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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
OR10Z1	NM_001004478.2 linkuse as main transcript	c.3786_3787insACACAT		3_prime_UTR_variant	2/2	ENST00000641002.1
SPTA1	NM_003126.4 linkuse as main transcript	c.97_98insATGTGT		3_prime_UTR_variant	52/52	ENST00000643759.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR10Z1	ENST00000641002.1 linkuse as main transcript	c.3786_3787insACACAT	3_prime_UTR_variant	2/2		NM_001004478.2	P1
SPTA1	ENST00000643759.2 linkuse as main transcript	c.97_98insATGTGT	3_prime_UTR_variant	52/52		NM_003126.4	P1	P02549-1
SPTA1	ENST00000485680.1 linkuse as main transcript		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00208

AC:

307

AN:

147330

Hom.:

Cov.:

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.:

Cov.:

AF XY:

0.000153

AC XY:

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.:

Cov.:

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 submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Pyropoikilocytosis, hereditary

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Spherocytosis, Recessive

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over