6-134978710-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006620.4(HBS1L):āc.1766A>Gā(p.Asn589Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000437 in 1,602,676 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.0000041 ( 0 hom. )
Consequence
HBS1L
NM_006620.4 missense
NM_006620.4 missense
Scores
3
6
10
Clinical Significance
Conservation
PhyloP100: 8.02
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]
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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/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HBS1L | NM_006620.4 | c.1766A>G | p.Asn589Ser | missense_variant | 15/18 | ENST00000367837.10 | NP_006611.1 | |
HBS1L | NM_001145158.2 | c.1640A>G | p.Asn547Ser | missense_variant | 14/17 | NP_001138630.1 | ||
HBS1L | NM_001363686.2 | c.1274A>G | p.Asn425Ser | missense_variant | 16/19 | NP_001350615.1 | ||
HBS1L | XM_047418093.1 | c.1766A>G | p.Asn589Ser | missense_variant | 15/16 | XP_047274049.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HBS1L | ENST00000367837.10 | c.1766A>G | p.Asn589Ser | missense_variant | 15/18 | 1 | NM_006620.4 | ENSP00000356811 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151962Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000202 AC: 5AN: 247220Hom.: 0 AF XY: 0.0000299 AC XY: 4AN XY: 133756
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GnomAD4 exome AF: 0.00000414 AC: 6AN: 1450714Hom.: 0 Cov.: 28 AF XY: 0.00000416 AC XY: 3AN XY: 721860
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 151962Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74224
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 17, 2023 | The c.1766A>G (p.N589S) alteration is located in exon 15 (coding exon 15) of the HBS1L gene. This alteration results from a A to G substitution at nucleotide position 1766, causing the asparagine (N) at amino acid position 589 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
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
Benign
L;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D
REVEL
Uncertain
Sift
Benign
T;T;T;T;T
Sift4G
Benign
T;T;T;T;T
Polyphen
D;.;.;D;.
Vest4
MutPred
Gain of sheet (P = 0.1208);.;.;.;.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at