NM_003126.4:c.*125_*132dupTGTGTGTG

Variant names:

• chr1-158611131-G-GCACACACA
• rs55832242
• NM_003126.4:c.*125_*132dupTGTGTGTG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_003126.4(SPTA1):​c.*125_*132dupTGTGTGTG 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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003126.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTA1	NM_003126.4	MANE Select	c.*125_*132dupTGTGTGTG		3_prime_UTR	Exon 52 of 52	NP_003117.2	P02549-1
	OR10Z1	NM_001004478.2	MANE Select	c.*3779_*3786dupACACACAC		3_prime_UTR	Exon 2 of 2	NP_001004478.1	A0A126GV63

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTA1	ENST00000643759.2	MANE Select	c.*125_*132dupTGTGTGTG		3_prime_UTR	Exon 52 of 52	ENSP00000495214.1	P02549-1
	OR10Z1	ENST00000641002.1	MANE Select	c.*3779_*3786dupACACACAC		3_prime_UTR	Exon 2 of 2	ENSP00000493003.1	Q8NGY1
	SPTA1	ENST00000485680.1	TSL:3	n.*69_*76dupTGTGTGTG		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0787 AC: 11310 AN: 143714 Hom.: 501 Cov.: 0

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

African (AFR) AF: 0.0749 AC: 1117 AN: 14914

American (AMR) AF: 0.0469 AC: 1373 AN: 29248

Ashkenazi Jewish (ASJ) AF: 0.0999 AC: 1507 AN: 15082

East Asian (EAS) AF: 0.0275 AC: 714 AN: 25962

South Asian (SAS) AF: 0.0509 AC: 2784 AN: 54684

European-Finnish (FIN) AF: 0.0748 AC: 2261 AN: 30226

Middle Eastern (MID) AF: 0.0673 AC: 155 AN: 2304

European-Non Finnish (NFE) AF: 0.0659 AC: 21396 AN: 324782

Other (OTH) AF: 0.0629 AC: 1663 AN: 26428

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

African (AFR) AF: 0.0950 AC: 3654 AN: 38474

American (AMR) AF: 0.0616 AC: 882 AN: 14316

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 388 AN: 3378

East Asian (EAS) AF: 0.0130 AC: 63 AN: 4844

South Asian (SAS) AF: 0.0431 AC: 191 AN: 4428

European-Finnish (FIN) AF: 0.0898 AC: 825 AN: 9184

Middle Eastern (MID) AF: 0.165 AC: 46 AN: 278

European-Non Finnish (NFE) AF: 0.0761 AC: 5029 AN: 66058

Other (OTH) AF: 0.0768 AC: 151 AN: 1966

Alfa AF: 0.0823 Hom.: 292

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Elliptocytosis (1)
-	1	-	Pyropoikilocytosis, hereditary (1)
-	1	-	Spherocytosis, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs55832242; hg19: chr1-158580921;