6-134985353-C-T
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006620.4(HBS1L):c.1480G>A(p.Asp494Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000998 in 1,603,588 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00010 ( 0 hom. )
Consequence
HBS1L
NM_006620.4 missense
NM_006620.4 missense
Scores
7
5
7
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.12
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HBS1L | NM_006620.4 | c.1480G>A | p.Asp494Asn | missense_variant | Exon 12 of 18 | ENST00000367837.10 | NP_006611.1 | |
HBS1L | NM_001145158.2 | c.1354G>A | p.Asp452Asn | missense_variant | Exon 11 of 17 | NP_001138630.1 | ||
HBS1L | NM_001363686.2 | c.988G>A | p.Asp330Asn | missense_variant | Exon 13 of 19 | NP_001350615.1 | ||
HBS1L | XM_047418093.1 | c.1480G>A | p.Asp494Asn | missense_variant | Exon 12 of 16 | XP_047274049.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000989 AC: 15AN: 151698Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
15
AN:
151698
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: 0.0000244 AC: 6AN: 246318Hom.: 0 AF XY: 0.0000375 AC XY: 5AN XY: 133310
GnomAD3 exomes
AF:
AC:
6
AN:
246318
Hom.:
AF XY:
AC XY:
5
AN XY:
133310
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: 0.0000999 AC: 145AN: 1451890Hom.: 0 Cov.: 28 AF XY: 0.0000900 AC XY: 65AN XY: 722618
GnomAD4 exome
AF:
AC:
145
AN:
1451890
Hom.:
Cov.:
28
AF XY:
AC XY:
65
AN XY:
722618
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: 0.0000989 AC: 15AN: 151698Hom.: 0 Cov.: 32 AF XY: 0.0000675 AC XY: 5AN XY: 74052
GnomAD4 genome
AF:
AC:
15
AN:
151698
Hom.:
Cov.:
32
AF XY:
AC XY:
5
AN XY:
74052
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:
ExAC
AF:
AC:
4
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T;T;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D;D
Sift4G
Benign
T;T;T;T;T
Polyphen
D;.;.;D;.
Vest4
MutPred
Gain of sheet (P = 0.0827);.;.;.;.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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