NM_003126.4:c.*295C>T

Variant names:

• chr1-158610969-G-A
• rs12601
• NM_003126.4:c.*295C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003126.4(SPTA1):​c.*295C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 309,906 control chromosomes in the GnomAD database, including 44,059 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (21092 hom., cov: 31)
  • Exomes 𝑓: 0.53 (22967 hom.)
• Consequence: SPTA1 NM_003126.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.104
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 1-158610969-G-A is Benign according to our data. Variant chr1-158610969-G-A is described in ClinVar as Benign. ClinVar VariationId is 292920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 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.*295C>T		3_prime_UTR	Exon 52 of 52	NP_003117.2	P02549-1
	OR10Z1	NM_001004478.2	MANE Select	c.*3589G>A		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.*295C>T		3_prime_UTR	Exon 52 of 52	ENSP00000495214.1	P02549-1
	OR10Z1	ENST00000641002.1	MANE Select	c.*3589G>A		3_prime_UTR	Exon 2 of 2	ENSP00000493003.1	Q8NGY1
	SPTA1	ENST00000485680.1	TSL:3	n.*239C>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79215 AN: 151738 Hom.: 21066 Cov.: 31

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.537

GnomAD4 exome AF: 0.533 AC: 84218 AN: 158050 Hom.: 22967 Cov.: 2 AF XY: 0.524 AC XY: 43938 AN XY: 83832

African (AFR) AF: 0.411 AC: 2088 AN: 5076

American (AMR) AF: 0.529 AC: 3655 AN: 6904

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 2589 AN: 4558

East Asian (EAS) AF: 0.597 AC: 5884 AN: 9858

South Asian (SAS) AF: 0.420 AC: 8630 AN: 20558

European-Finnish (FIN) AF: 0.613 AC: 4628 AN: 7554

Middle Eastern (MID) AF: 0.533 AC: 358 AN: 672

European-Non Finnish (NFE) AF: 0.548 AC: 51550 AN: 94022

Other (OTH) AF: 0.547 AC: 4836 AN: 8848

GnomAD4 genome AF: 0.522 AC: 79290 AN: 151856 Hom.: 21092 Cov.: 31 AF XY: 0.528 AC XY: 39182 AN XY: 74182

African (AFR) AF: 0.424 AC: 17568 AN: 41392

American (AMR) AF: 0.544 AC: 8288 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1977 AN: 3470

East Asian (EAS) AF: 0.625 AC: 3232 AN: 5174

South Asian (SAS) AF: 0.435 AC: 2089 AN: 4806

European-Finnish (FIN) AF: 0.639 AC: 6741 AN: 10550

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.553 AC: 37568 AN: 67924

Other (OTH) AF: 0.542 AC: 1144 AN: 2110

Alfa AF: 0.538 Hom.: 12152

Bravo AF: 0.515

Asia WGS AF: 0.558 AC: 1940 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Elliptocytosis 2 (1)
-	-	1	Hereditary spherocytosis type 3 (1)
-	-	1	Pyropoikilocytosis, hereditary (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.0
DANN	Benign	0.52
PhyloP100		0.10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs12601; hg19: chr1-158580759;