rs142775522
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_003126.4(SPTA1):c.6672A>C(p.Glu2224Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000898 in 1,614,124 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0046 ( 4 hom., cov: 32)
Exomes 𝑓: 0.00051 ( 6 hom. )
Consequence
SPTA1
NM_003126.4 missense
NM_003126.4 missense
Scores
2
4
10
Clinical Significance
Conservation
PhyloP100: 0.202
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0067679286).
BP6
Variant 1-158615332-T-G is Benign according to our data. Variant chr1-158615332-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 258956.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00461 (703/152330) while in subpopulation AFR AF= 0.0163 (676/41580). AF 95% confidence interval is 0.0152. There are 4 homozygotes in gnomad4. There are 334 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 4 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SPTA1 | NM_003126.4 | c.6672A>C | p.Glu2224Asp | missense_variant | 48/52 | ENST00000643759.2 | NP_003117.2 | |
SPTA1 | XM_011509916.3 | c.6672A>C | p.Glu2224Asp | missense_variant | 49/53 | XP_011508218.1 | ||
SPTA1 | XM_011509917.4 | c.6654A>C | p.Glu2218Asp | missense_variant | 47/51 | XP_011508219.1 | ||
SPTA1 | XM_047428883.1 | c.6351A>C | p.Glu2117Asp | missense_variant | 48/52 | XP_047284839.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SPTA1 | ENST00000643759.2 | c.6672A>C | p.Glu2224Asp | missense_variant | 48/52 | NM_003126.4 | ENSP00000495214 | P1 | ||
SPTA1 | ENST00000492934.1 | n.187A>C | non_coding_transcript_exon_variant | 3/3 | 2 | |||||
SPTA1 | ENST00000498708.1 | n.104A>C | non_coding_transcript_exon_variant | 2/5 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00458 AC: 697AN: 152212Hom.: 4 Cov.: 32
GnomAD3 genomes
AF:
AC:
697
AN:
152212
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00111 AC: 278AN: 249558Hom.: 0 AF XY: 0.000835 AC XY: 113AN XY: 135396
GnomAD3 exomes
AF:
AC:
278
AN:
249558
Hom.:
AF XY:
AC XY:
113
AN XY:
135396
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000510 AC: 746AN: 1461794Hom.: 6 Cov.: 31 AF XY: 0.000446 AC XY: 324AN XY: 727196
GnomAD4 exome
AF:
AC:
746
AN:
1461794
Hom.:
Cov.:
31
AF XY:
AC XY:
324
AN XY:
727196
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00461 AC: 703AN: 152330Hom.: 4 Cov.: 32 AF XY: 0.00448 AC XY: 334AN XY: 74494
GnomAD4 genome
AF:
AC:
703
AN:
152330
Hom.:
Cov.:
32
AF XY:
AC XY:
334
AN XY:
74494
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
55
ESP6500EA
AF:
AC:
0
ExAC
AF:
AC:
160
Asia WGS
AF:
AC:
1
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Pathogenic:1Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 31, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2022 | SPTA1: BP4, BS1, BS2 - |
Familial hemolytic anemia Pathogenic:1
Likely pathogenic, flagged submission | clinical testing | Department of Genetic, Henri Mondor Hospital, Assistance Publique des Hôpitaux de Paris | Feb 27, 2018 | - - |
Elliptocytosis 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
.;D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Benign
T
REVEL
Benign
Sift4G
Pathogenic
D;.
Polyphen
D;D
Vest4
MutPred
Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at