1-158611131-GCACACACACACACACACACACA-GCACACACACACACACACACACACACACACACA

Variant names:

• chr1-158611131-G-GCACACACACA
• rs55832242
• NM_003126.4:c.*123_*132dupTGTGTGTGTG

Variant summary

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

The NM_003126.4(SPTA1):​c.*123_*132dupTGTGTGTGTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1124 hom., cov: 0)
  • Exomes 𝑓: 0.090 (671 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPTA1 NM_003126.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTA1	NM_003126.4	c.*123_*132dupTGTGTGTGTG		3_prime_UTR_variant	Exon 52 of 52	ENST00000643759.2	NP_003117.2
OR10Z1	NM_001004478.2	c.*3777_*3786dupACACACACAC		3_prime_UTR_variant	Exon 2 of 2	ENST00000641002.1	NP_001004478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTA1	ENST00000643759	c.*123_*132dupTGTGTGTGTG		3_prime_UTR_variant	Exon 52 of 52		NM_003126.4	ENSP00000495214.1
OR10Z1	ENST00000641002.1	c.*3777_*3786dupACACACACAC		3_prime_UTR_variant	Exon 2 of 2		NM_001004478.2	ENSP00000493003.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 17352 AN: 143656 Hom.: 1124 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0806

Gnomad AMI AF: 0.0871

Gnomad AMR AF: 0.0944

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.116

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.119

GnomAD4 exome AF: 0.0901 AC: 47136 AN: 523080 Hom.: 671 Cov.: 0 AF XY: 0.0912 AC XY: 25316 AN XY: 277552

Gnomad4 AFR exome AF: 0.0572

Gnomad4 AMR exome AF: 0.0673

Gnomad4 ASJ exome AF: 0.0786

Gnomad4 EAS exome AF: 0.116

Gnomad4 SAS exome AF: 0.100

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.0899

Gnomad4 OTH exome AF: 0.0849

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.121 AC: 17364 AN: 143766 Hom.: 1124 Cov.: 0 AF XY: 0.122 AC XY: 8477 AN XY: 69490

Gnomad4 AFR AF: 0.0805

Gnomad4 AMR AF: 0.0945

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.122

ClinVar

Not reported in ClinVar

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;