dbSNP rs112702237: HBS1L:p.Ser65Phe (chr6-135042042-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006620.4(HBS1L):c.194C>T(p.Ser65Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000281 in 1,613,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

HBS1L
NM_006620.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.67

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]

HBS1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2020933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HBS1L	NM_006620.4 link	c.194C>T	p.Ser65Phe	missense_variant	Exon 3 of 18	ENST00000367837.10	NP_006611.1	Q9Y450-1D9YZV0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBS1L	ENST00000367837.10 link	c.194C>T	p.Ser65Phe	missense_variant	Exon 3 of 18	1	NM_006620.4	ENSP00000356811.5		Q9Y450-1

Frequencies

GnomAD3 genomes

AF:

0.000178

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000131

AC:

AN:

251066

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

135714

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:

0.000282

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000292

AC:

426

AN:

1461088

Hom.:

Cov.:

AF XY:

0.000294

AC XY:

214

AN XY:

726852

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000563

Gnomad4 NFE exome

AF:

0.000367

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.000177

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000631

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.000165

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;T;T;T;.;.;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.78

T;T;T;T;T;T;T

M_CAP

Benign

0.061

MetaRNN

Benign

0.20

T;T;T;T;T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.1

M;.;.;.;.;M;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.1

N;N;D;D;D;D;D

REVEL

Uncertain

0.29

Sift

Uncertain

0.0060

D;D;D;D;D;D;D

Sift4G

Benign

0.16

T;D;D;.;.;D;D

Polyphen

0.68

P;.;.;.;.;P;.

Vest4

0.36

MVP

0.67

MPC

0.28

ClinPred

0.18

GERP RS

5.8

Varity_R

0.081

gMVP

0.35

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over