rs1187224134

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_006620.4(HBS1L):ā€‹c.1067T>Gā€‹(p.Ile356Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,421,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 7.0e-7 ( 0 hom. )

Consequence

HBS1L
NM_006620.4 missense

Scores

14
3
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.32
Variant links:
Genes affected
HBS1L (HGNC:4834): (HBS1 like translational GTPase) This gene encodes a member of the GTP-binding elongation factor family. It is expressed in multiple tissues with the highest expression in heart and skeletal muscle. The intergenic region of this gene and the MYB gene has been identified to be a quantitative trait locus (QTL) controlling fetal hemoglobin level, and this region influnces erythrocyte, platelet, and monocyte counts as well as erythrocyte volume and hemoglobin content. DNA polymorphisms at this region associate with fetal hemoglobin levels and pain crises in sickle cell disease. A single nucleotide polymorphism in exon 1 of this gene is significantly associated with severity in beta-thalassemia/Hemoglobin E. Multiple alternatively spliced transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, May 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.948

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HBS1LNM_006620.4 linkc.1067T>G p.Ile356Ser missense_variant Exon 8 of 18 ENST00000367837.10 NP_006611.1 Q9Y450-1D9YZV0
HBS1LNM_001145158.2 linkc.941T>G p.Ile314Ser missense_variant Exon 7 of 17 NP_001138630.1 Q9Y450-4
HBS1LNM_001363686.2 linkc.575T>G p.Ile192Ser missense_variant Exon 9 of 19 NP_001350615.1
HBS1LXM_047418093.1 linkc.1067T>G p.Ile356Ser missense_variant Exon 8 of 16 XP_047274049.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HBS1LENST00000367837.10 linkc.1067T>G p.Ile356Ser missense_variant Exon 8 of 18 1 NM_006620.4 ENSP00000356811.5 Q9Y450-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000404
AC:
1
AN:
247444
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
133902
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:
0.00000891
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
7.04e-7
AC:
1
AN:
1421378
Hom.:
0
Cov.:
26
AF XY:
0.00
AC XY:
0
AN XY:
707570
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:
9.23e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.000111
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.39
D
BayesDel_noAF
Pathogenic
0.32
CADD
Pathogenic
32
DANN
Uncertain
0.99
DEOGEN2
Benign
0.37
T;T;T;.;T;.
Eigen
Pathogenic
1.1
Eigen_PC
Pathogenic
1.0
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.98
D;D;D;D;D;D
M_CAP
Pathogenic
0.36
D
MetaRNN
Pathogenic
0.95
D;D;D;D;D;D
MetaSVM
Uncertain
0.58
D
MutationAssessor
Uncertain
2.1
M;.;.;.;.;.
PrimateAI
Pathogenic
0.90
D
PROVEAN
Pathogenic
-5.9
D;D;D;D;D;D
REVEL
Pathogenic
0.73
Sift
Pathogenic
0.0
D;D;D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D;D;D
Polyphen
1.0
D;.;.;D;.;.
Vest4
0.98
MutPred
0.83
Gain of disorder (P = 0.0283);.;.;.;.;.;
MVP
0.89
MPC
0.83
ClinPred
1.0
D
GERP RS
6.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.95
gMVP
0.98

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: rs1187224134; hg19: chr6-135314912; API