NM_003126.4:c.*295C>G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003126.4(SPTA1):​c.*295C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPTA1 NM_003126.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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>G		3_prime_UTR	Exon 52 of 52	NP_003117.2	P02549-1
	OR10Z1	NM_001004478.2	MANE Select	c.*3589G>C		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>G		3_prime_UTR	Exon 52 of 52	ENSP00000495214.1	P02549-1
	OR10Z1	ENST00000641002.1	MANE Select	c.*3589G>C		3_prime_UTR	Exon 2 of 2	ENSP00000493003.1	Q8NGY1
	SPTA1	ENST00000485680.1	TSL:3	n.*239C>G		downstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 158838 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 84262

African (AFR) AF: 0.00 AC: 0 AN: 5106

American (AMR) AF: 0.00 AC: 0 AN: 6934

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4592

East Asian (EAS) AF: 0.00 AC: 0 AN: 9900

South Asian (SAS) AF: 0.00 AC: 0 AN: 20662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 684

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 94476

Other (OTH) AF: 0.00 AC: 0 AN: 8898

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.37
PhyloP100		0.10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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;