Variant chr1-158611131-G-GCACACA 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_*133insTGTGTG 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 0.036 ( 101 hom., cov: 0)

Exomes 𝑓: 0.037 ( 140 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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0363 (5218/143874) while in subpopulation AMR AF= 0.039 (558/14320). AF 95% confidence interval is 0.0376. There are 101 homozygotes in gnomad4. There are 2566 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 101 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR10Z1	NM_001004478.2 linkuse as main transcript	c.3781_3786dup		3_prime_UTR_variant	2/2	ENST00000641002.1
SPTA1	NM_003126.4 linkuse as main transcript	c.132_133insTGTGTG		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.3781_3786dup		3_prime_UTR_variant	2/2		NM_001004478.2	P1
SPTA1	ENST00000643759.2 linkuse as main transcript	c.132_133insTGTGTG		3_prime_UTR_variant	52/52		NM_003126.4	P1	P02549-1

Frequencies

GnomAD3 genomes

AF:

0.0364

AC:

5228

AN:

143764

Hom.:

101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0312

Gnomad AMI

AF:

0.0424

Gnomad AMR

AF:

0.0391

Gnomad ASJ

AF:

0.0388

Gnomad EAS

AF:

0.0105

Gnomad SAS

AF:

0.0205

Gnomad FIN

AF:

0.0549

Gnomad MID

AF:

0.0464

Gnomad NFE

AF:

0.0389

Gnomad OTH

AF:

0.0348

GnomAD4 exome

AF:

0.0368

AC:

19313

AN:

524942

Hom.:

140

Cov.:

AF XY:

0.0363

AC XY:

10107

AN XY:

278578

show subpopulations

Gnomad4 AFR exome

AF:

0.0344

Gnomad4 AMR exome

AF:

0.0286

Gnomad4 ASJ exome

AF:

0.0491

Gnomad4 EAS exome

AF:

0.0149

Gnomad4 SAS exome

AF:

0.0250

Gnomad4 FIN exome

AF:

0.0605

Gnomad4 NFE exome

AF:

0.0383

Gnomad4 OTH exome

AF:

0.0398

GnomAD4 genome

AF:

0.0363

AC:

5218

AN:

143874

Hom.:

101

Cov.:

AF XY:

0.0369

AC XY:

2566

AN XY:

69556

show subpopulations

Gnomad4 AFR

AF:

0.0311

Gnomad4 AMR

AF:

0.0390

Gnomad4 ASJ

AF:

0.0388

Gnomad4 EAS

AF:

0.0103

Gnomad4 SAS

AF:

0.0203

Gnomad4 FIN

AF:

0.0549

Gnomad4 NFE

AF:

0.0389

Gnomad4 OTH

AF:

0.0345

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