rs1555367359

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_001355436.2(SPTB):​c.5623C>T​(p.Gln1875Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)

Consequence

SPTB
NM_001355436.2 stop_gained

Scores

5
1
1

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 7.97
Variant links:
Genes affected
SPTB (HGNC:11274): (spectrin beta, erythrocytic) This locus encodes a member of the spectrin gene family. Spectrin proteins, along with ankyrin, play a role in cell membrane organization and stability. The protein encoded by this locus functions in stability of erythrocyte membranes, and mutations in this gene have been associated with spherocytosis type 2, hereditary elliptocytosis, and neonatal hemolytic anemia. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2009]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 14-64771060-G-A is Pathogenic according to our data. Variant chr14-64771060-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 544817.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SPTBNM_001355436.2 linkuse as main transcriptc.5623C>T p.Gln1875Ter stop_gained 27/36 ENST00000644917.1 NP_001342365.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SPTBENST00000644917.1 linkuse as main transcriptc.5623C>T p.Gln1875Ter stop_gained 27/36 NM_001355436.2 ENSP00000495909 P1P11277-2
SPTBENST00000553938.5 linkuse as main transcriptc.1618C>T p.Gln540Ter stop_gained 8/181 ENSP00000451324
SPTBENST00000389722.7 linkuse as main transcriptc.5623C>T p.Gln1875Ter stop_gained 26/352 ENSP00000374372 P1P11277-2
SPTBENST00000389720.4 linkuse as main transcriptc.5623C>T p.Gln1875Ter stop_gained 27/325 ENSP00000374370 P11277-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Hereditary spherocytosis type 2 Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingDepartment of Genetic, Henri Mondor Hospital, Assistance Publique des Hôpitaux de ParisFeb 27, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.61
D
BayesDel_noAF
Pathogenic
0.63
CADD
Pathogenic
48
DANN
Uncertain
1.0
Eigen
Pathogenic
0.94
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Pathogenic
0.99
D
MutationTaster
Benign
1.0
A;A;A;A;A
Vest4
0.83
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8

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.

Other links and lift over

dbSNP: rs1555367359; hg19: chr14-65237778; API