6-134985353-C-T

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

Scores

7
5
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.12
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 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
HBS1LNM_006620.4 linkc.1480G>A p.Asp494Asn missense_variant Exon 12 of 18 ENST00000367837.10 NP_006611.1 Q9Y450-1D9YZV0
HBS1LNM_001145158.2 linkc.1354G>A p.Asp452Asn missense_variant Exon 11 of 17 NP_001138630.1 Q9Y450-4
HBS1LNM_001363686.2 linkc.988G>A p.Asp330Asn missense_variant Exon 13 of 19 NP_001350615.1
HBS1LXM_047418093.1 linkc.1480G>A p.Asp494Asn missense_variant Exon 12 of 16 XP_047274049.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HBS1LENST00000367837.10 linkc.1480G>A p.Asp494Asn missense_variant Exon 12 of 18 1 NM_006620.4 ENSP00000356811.5 Q9Y450-1

Frequencies

GnomAD3 genomes
AF:
0.0000989
AC:
15
AN:
151698
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000657
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000244
AC:
6
AN:
246318
Hom.:
0
AF XY:
0.0000375
AC XY:
5
AN XY:
133310
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:
0.0000338
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000445
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000999
AC:
145
AN:
1451890
Hom.:
0
Cov.:
28
AF XY:
0.0000900
AC XY:
65
AN XY:
722618
show subpopulations
Gnomad4 AFR exome
AF:
0.0000304
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000127
Gnomad4 SAS exome
AF:
0.0000826
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000116
Gnomad4 OTH exome
AF:
0.0000668
GnomAD4 genome
AF:
0.0000989
AC:
15
AN:
151698
Hom.:
0
Cov.:
32
AF XY:
0.0000675
AC XY:
5
AN XY:
74052
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.0000657
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000558
Hom.:
0
Bravo
AF:
0.0000831
ExAC
AF:
0.0000330
AC:
4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.80
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.38
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.31
T;T;T;.;T
Eigen
Pathogenic
0.89
Eigen_PC
Pathogenic
0.86
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.97
D;D;D;D;D
M_CAP
Benign
0.053
D
MetaRNN
Uncertain
0.67
D;D;D;D;D
MetaSVM
Benign
-0.45
T
MutationAssessor
Uncertain
2.3
M;.;.;.;.
PrimateAI
Uncertain
0.75
T
PROVEAN
Pathogenic
-5.0
D;D;D;D;D
REVEL
Uncertain
0.41
Sift
Pathogenic
0.0
D;D;D;D;D
Sift4G
Benign
0.062
T;T;T;T;T
Polyphen
1.0
D;.;.;D;.
Vest4
0.92
MutPred
0.64
Gain of sheet (P = 0.0827);.;.;.;.;
MVP
0.69
MPC
0.67
ClinPred
0.87
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.73
gMVP
0.70

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: rs767321403; hg19: chr6-135306491; COSMIC: COSV100892612; COSMIC: COSV100892612; API