Variant rs121918638 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PP3_StrongPP5_Moderate

The NM_003126.4(SPTA1):c.137G>T(p.Gly46Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000144 in 1,461,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

SPTA1
NM_003126.4 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 4.75

Variant links:

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]

SPTA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PM1

In a helix (size 43) in uniprot entity SPTA1_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_003126.4

PP3

MetaRNN computational evidence supports a deleterious effect, 0.94

PP5

Variant 1-158685235-C-A is Pathogenic according to our data. Variant chr1-158685235-C-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 12850.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTA1	NM_003126.4 linkuse as main transcript	c.137G>T	p.Gly46Val	missense_variant	2/52	ENST00000643759.2	NP_003117.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTA1	ENST00000643759.2 linkuse as main transcript	c.137G>T	p.Gly46Val	missense_variant	2/52		NM_003126.4	ENSP00000495214	P1	P02549-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000811

AC:

AN:

246758

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134086

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000181

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461552

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727070

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Elliptocytosis 2

Pathogenic:2

Pathogenic, no assertion criteria provided	literature only	OMIM	Aug 01, 1990	- -
Likely pathogenic, criteria provided, single submitter	clinical testing	Bioinformatics dept., Datar Cancer Genetics Limited, India	Jun 23, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Uncertain

0.034

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.56

D;D

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.94

.;D

M_CAP

Benign

0.048

MetaRNN

Pathogenic

0.94

D;D

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

1.0

A;A

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.4

N;.

REVEL

Benign

0.25

Sift

Uncertain

0.019

D;.

Sift4G

Benign

0.21

T;.

Polyphen

0.98

D;D

Vest4

0.57

MutPred

0.83

Loss of ubiquitination at K48 (P = 0.063);Loss of ubiquitination at K48 (P = 0.063);

MVP

0.73

MPC

0.23

ClinPred

0.91

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.74

gMVP

0.29

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

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