1-158611131-G-GCA

Position:

• chr1-158611131-G-GCA

Variant summary

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

The NM_003126.4(SPTA1):​c.*132_*133insTG 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 0.046 (164 hom., cov: 0)
  • Exomes 𝑓: 0.052 (48 hom.)
• 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: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR10Z1	NM_001004478.2	c.*3785_*3786dup		3_prime_UTR_variant	2/2	ENST00000641002.1
SPTA1	NM_003126.4	c.*132_*133insTG		3_prime_UTR_variant	52/52	ENST00000643759.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR10Z1	ENST00000641002.1	c.*3785_*3786dup		3_prime_UTR_variant	2/2		NM_001004478.2	P1
SPTA1	ENST00000643759.2	c.*132_*133insTG		3_prime_UTR_variant	52/52		NM_003126.4	P1

Frequencies

GnomAD3 genomes AF: 0.0458 AC: 6580 AN: 143730 Hom.: 163 Cov.: 0

Gnomad AFR AF: 0.0452

Gnomad AMI AF: 0.0357

Gnomad AMR AF: 0.0364

Gnomad ASJ AF: 0.0474

Gnomad EAS AF: 0.0551

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0516

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0413

Gnomad OTH AF: 0.0564

GnomAD4 exome AF: 0.0519 AC: 27193 AN: 523588 Hom.: 48 Cov.: 0 AF XY: 0.0550 AC XY: 15289 AN XY: 277776

Gnomad4 AFR exome AF: 0.0507

Gnomad4 AMR exome AF: 0.0284

Gnomad4 ASJ exome AF: 0.0446

Gnomad4 EAS exome AF: 0.0700

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.0499

Gnomad4 NFE exome AF: 0.0443

Gnomad4 OTH exome AF: 0.0523

GnomAD4 genome AF: 0.0458 AC: 6585 AN: 143840 Hom.: 164 Cov.: 0 AF XY: 0.0475 AC XY: 3302 AN XY: 69534

Gnomad4 AFR AF: 0.0453

Gnomad4 AMR AF: 0.0363

Gnomad4 ASJ AF: 0.0474

Gnomad4 EAS AF: 0.0550

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0516

Gnomad4 NFE AF: 0.0414

Gnomad4 OTH AF: 0.0553

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;