16-180841-C-G

Variant summary

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

The NM_005331.5(HBQ1):​c.271C>G​(p.Gln91Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,391,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

HBQ1
NM_005331.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.302
Variant links:
Genes affected
HBQ1 (HGNC:4833): (hemoglobin subunit theta 1) Theta-globin mRNA is found in human fetal erythroid tissue but not in adult erythroid or other nonerythroid tissue. The theta-1 gene may be expressed very early in embryonic life, perhaps sometime before 5 weeks. Theta-1 is a member of the human alpha-globin gene cluster that involves five functional genes and two pseudogenes. The order of genes is: 5' - zeta - pseudozeta - mu - pseudoalpha-2 -pseudoalpha-1 - alpha-2 - alpha-1 - theta-1 - 3'. Research supports a transcriptionally active role for the gene and a functional role for the peptide in specific cells, possibly those of early erythroid tissue. [provided by RefSeq, Jul 2008]

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=0.07355407).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HBQ1NM_005331.5 linkc.271C>G p.Gln91Glu missense_variant Exon 2 of 3 ENST00000199708.3 NP_005322.1 P09105A0A1K0GUV5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HBQ1ENST00000199708.3 linkc.271C>G p.Gln91Glu missense_variant Exon 2 of 3 1 NM_005331.5 ENSP00000199708.2 P09105

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.19e-7
AC:
1
AN:
1391502
Hom.:
0
Cov.:
34
AF XY:
0.00000146
AC XY:
1
AN XY:
687190
show subpopulations
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 21, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.271C>G (p.Q91E) alteration is located in exon 2 (coding exon 2) of the HBQ1 gene. This alteration results from a C to G substitution at nucleotide position 271, causing the glutamine (Q) at amino acid position 91 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.086
BayesDel_addAF
Benign
-0.085
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
0.18
DANN
Benign
0.43
DEOGEN2
Benign
0.058
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.081
N
LIST_S2
Benign
0.79
T
M_CAP
Benign
0.067
D
MetaRNN
Benign
0.074
T
MetaSVM
Benign
-0.60
T
MutationAssessor
Benign
-0.21
N
PrimateAI
Benign
0.40
T
PROVEAN
Benign
0.060
N
REVEL
Benign
0.23
Sift
Benign
0.047
D
Sift4G
Benign
0.19
T
Polyphen
0.0
B
Vest4
0.12
MutPred
0.49
Gain of catalytic residue at Q91 (P = 0.2656);
MVP
0.52
MPC
0.81
ClinPred
0.12
T
GERP RS
-2.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.072
gMVP
0.096

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: chr16-230840; API