1-158611131-G-GCACACACA

Position:

• chr1-158611131-G-GCACACACA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_003126.4(SPTA1):​c.*132_*133insTGTGTGTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.079 (501 hom., cov: 0)
  • Exomes 𝑓: 0.063 (397 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPTA1 NM_003126.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:3
• Conservation: PhyloP100: 0.00

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR10Z1	NM_001004478.2	c.*3779_*3786dup		3_prime_UTR_variant	2/2	ENST00000641002.1
SPTA1	NM_003126.4	c.*132_*133insTGTGTGTG		3_prime_UTR_variant	52/52	ENST00000643759.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR10Z1	ENST00000641002.1	c.*3779_*3786dup		3_prime_UTR_variant	2/2		NM_001004478.2	P1
SPTA1	ENST00000643759.2	c.*132_*133insTGTGTGTG		3_prime_UTR_variant	52/52		NM_003126.4	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 11310 AN: 143714 Hom.: 501 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0951

Gnomad AMI AF: 0.0915

Gnomad AMR AF: 0.0618

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0132

Gnomad SAS AF: 0.0438

Gnomad FIN AF: 0.0898

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.0761

Gnomad OTH AF: 0.0775

GnomAD4 exome AF: 0.0630 AC: 32970 AN: 523630 Hom.: 397 Cov.: 0 AF XY: 0.0626 AC XY: 17392 AN XY: 277896

Gnomad4 AFR exome AF: 0.0749

Gnomad4 AMR exome AF: 0.0469

Gnomad4 ASJ exome AF: 0.0999

Gnomad4 EAS exome AF: 0.0275

Gnomad4 SAS exome AF: 0.0509

Gnomad4 FIN exome AF: 0.0748

Gnomad4 NFE exome AF: 0.0659

Gnomad4 OTH exome AF: 0.0629

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0786 AC: 11311 AN: 143822 Hom.: 501 Cov.: 0 AF XY: 0.0782 AC XY: 5438 AN XY: 69536

Gnomad4 AFR AF: 0.0950

Gnomad4 AMR AF: 0.0616

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.0130

Gnomad4 SAS AF: 0.0431

Gnomad4 FIN AF: 0.0898

Gnomad4 NFE AF: 0.0761

Gnomad4 OTH AF: 0.0768

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, single submitter

Submissions by phenotype

Elliptocytosis Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs55832242; hg19: chr1-158580921;