6-134978779-C-A

Variant names:

• chr6-134978779-C-A
• NM_006620.4:c.1697G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006620.4(HBS1L):​c.1697G>T​(p.Cys566Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000693 in 1,443,508 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: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: HBS1L NM_006620.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.03

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]

ACMG classification

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.1697G>T	p.Cys566Phe	missense_variant	Exon 15 of 18	ENST00000367837.10	NP_006611.1
HBS1L	NM_001145158.2	c.1571G>T	p.Cys524Phe	missense_variant	Exon 14 of 17		NP_001138630.1
HBS1L	NM_001363686.2	c.1205G>T	p.Cys402Phe	missense_variant	Exon 16 of 19		NP_001350615.1
HBS1L	XM_047418093.1	c.1697G>T	p.Cys566Phe	missense_variant	Exon 15 of 16		XP_047274049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBS1L	ENST00000367837.10	c.1697G>T	p.Cys566Phe	missense_variant	Exon 15 of 18	1	NM_006620.4	ENSP00000356811.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443508 Hom.: 0 Cov.: 27 AF XY: 0.00000139 AC XY: 1 AN XY: 718540

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: 0.0000120

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	22
DANN	Benign	0.87
DEOGEN2	Benign	0.22	T;T;T;.;T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.0071
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D;D;D;D;D
M_CAP	Benign	0.080	D
MetaRNN	Uncertain	0.51	D;D;D;D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.035	N;.;.;.;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.0	D;D;D;D;D
REVEL	Uncertain	0.36
Sift	Benign	0.20	T;T;T;T;T
Sift4G	Benign	0.68	T;T;T;T;T
Polyphen		0.86	P;.;.;P;.
Vest4		0.86
MutPred		0.43		Loss of ubiquitination at K561 (P = 0.1166);.;.;.;.;
MVP		0.45
MPC		0.74
ClinPred		0.90	D
GERP RS		5.0
Varity_R		0.30
gMVP		0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-135299917;