Variant chr1-158611131-G-GCACACACACACA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2

The NM_003126.4(SPTA1):c.*132_*133insTGTGTGTGTGTG 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 0.015 ( 35 hom., cov: 0)

Exomes 𝑓: 0.010 ( 35 hom. )

Consequence

SPTA1
NM_003126.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:3

Conservation

PhyloP100: 0.00

Variant links:

Genes affected

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]

OR10Z1 links:

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]

SPTA1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0147 (2109/143876) while in subpopulation SAS AF= 0.0341 (151/4424). AF 95% confidence interval is 0.0322. There are 35 homozygotes in gnomad4. There are 1012 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 35 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR10Z1	NM_001004478.2 linkuse as main transcript	c.3775_3786dup		3_prime_UTR_variant	2/2	ENST00000641002.1
SPTA1	NM_003126.4 linkuse as main transcript	c.132_133insTGTGTGTGTGTG		3_prime_UTR_variant	52/52	ENST00000643759.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR10Z1	ENST00000641002.1 linkuse as main transcript	c.3775_3786dup		3_prime_UTR_variant	2/2		NM_001004478.2	P1
SPTA1	ENST00000643759.2 linkuse as main transcript	c.132_133insTGTGTGTGTGTG		3_prime_UTR_variant	52/52		NM_003126.4	P1	P02549-1

Frequencies

GnomAD3 genomes

AF:

0.0146

AC:

2096

AN:

143766

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0336

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00587

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.0111

Gnomad SAS

AF:

0.0339

Gnomad FIN

AF:

0.00152

Gnomad MID

AF:

0.00331

Gnomad NFE

AF:

0.00640

Gnomad OTH

AF:

0.00922

GnomAD4 exome

AF:

0.0103

AC:

5441

AN:

526506

Hom.:

Cov.:

AF XY:

0.0114

AC XY:

3197

AN XY:

279414

show subpopulations

Gnomad4 AFR exome

AF:

0.0225

Gnomad4 AMR exome

AF:

0.00673

Gnomad4 ASJ exome

AF:

0.0132

Gnomad4 EAS exome

AF:

0.00971

Gnomad4 SAS exome

AF:

0.0278

Gnomad4 FIN exome

AF:

0.00387

Gnomad4 NFE exome

AF:

0.00762

Gnomad4 OTH exome

AF:

0.0108

GnomAD4 genome

AF:

0.0147

AC:

2109

AN:

143876

Hom.:

Cov.:

AF XY:

0.0146

AC XY:

1012

AN XY:

69552

show subpopulations

Gnomad4 AFR

AF:

0.0338

Gnomad4 AMR

AF:

0.00587

Gnomad4 ASJ

AF:

0.0187

Gnomad4 EAS

AF:

0.0114

Gnomad4 SAS

AF:

0.0341

Gnomad4 FIN

AF:

0.00152

Gnomad4 NFE

AF:

0.00640

Gnomad4 OTH

AF:

0.0101

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Elliptocytosis

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Pyropoikilocytosis, hereditary

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Spherocytosis, Recessive

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over