rs34122435

Variant names:

• chr1-158610763-TA-T
• rs34122435
• NM_003126.4:c.*500delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003126.4(SPTA1):​c.*500delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.047 in 152,718 control chromosomes in the GnomAD database, including 219 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.047 (218 hom., cov: 31)
  • Exomes 𝑓: 0.062 (1 hom.)
• Consequence: SPTA1 NM_003126.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 0.0510
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 1-158610763-TA-T is Benign according to our data. Variant chr1-158610763-TA-T is described in ClinVar as Likely_benign. ClinVar VariationId is 292917.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0659 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.*500delT		3_prime_UTR	Exon 52 of 52	NP_003117.2	P02549-1
	OR10Z1	NM_001004478.2	MANE Select	c.*3390delA		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.*500delT		3_prime_UTR	Exon 52 of 52	ENSP00000495214.1	P02549-1
	OR10Z1	ENST00000641002.1	MANE Select	c.*3390delA		3_prime_UTR	Exon 2 of 2	ENSP00000493003.1	Q8NGY1

Frequencies

GnomAD3 genomes AF: 0.0470 AC: 7143 AN: 152052 Hom.: 218 Cov.: 31

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0415

Gnomad ASJ AF: 0.0381

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0199

Gnomad FIN AF: 0.0988

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0675

Gnomad OTH AF: 0.0469

GnomAD4 exome AF: 0.0620 AC: 34 AN: 548 Hom.: 1 Cov.: 0 AF XY: 0.0852 AC XY: 23 AN XY: 270

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.0263 AC: 2 AN: 76

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 10

South Asian (SAS) AF: 0.0333 AC: 1 AN: 30

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0752 AC: 31 AN: 412

Other (OTH) AF: 0.00 AC: 0 AN: 14

GnomAD4 genome AF: 0.0469 AC: 7144 AN: 152170 Hom.: 218 Cov.: 31 AF XY: 0.0478 AC XY: 3557 AN XY: 74378

African (AFR) AF: 0.0115 AC: 477 AN: 41550

American (AMR) AF: 0.0415 AC: 633 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0381 AC: 132 AN: 3466

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5178

South Asian (SAS) AF: 0.0201 AC: 97 AN: 4818

European-Finnish (FIN) AF: 0.0988 AC: 1045 AN: 10572

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0675 AC: 4589 AN: 68002

Other (OTH) AF: 0.0464 AC: 98 AN: 2110

Alfa AF: 0.0548 Hom.: 36

Bravo AF: 0.0412

Asia WGS AF: 0.00754 AC: 26 AN: 3462

ClinVar

ClinVar submissions

Significance: Likely benign

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		0.051
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs34122435; hg19: chr1-158580553;