Genetic Variant NM_005331.5:c.217C>A (chr16-180787-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005331.5(HBQ1):c.217C>A(p.Arg73Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000425 in 1,413,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R73C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

HBQ1
NM_005331.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.938

Publications

1 publications found

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]

HBQ1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12561157).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005331.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBQ1	NM_005331.5	MANE Select	c.217C>A	p.Arg73Ser	missense	Exon 2 of 3	NP_005322.1	P09105

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBQ1	ENST00000199708.3	TSL:1 MANE Select	c.217C>A	p.Arg73Ser	missense	Exon 2 of 3	ENSP00000199708.2	P09105

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000590

AC:

AN:

169498

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000144

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000425

AC:

AN:

1413220

Hom.:

Cov.:

AF XY:

0.00000429

AC XY:

AN XY:

700092

show subpopulations

African (AFR)

AF:

0.0000310

AC:

AN:

32260

American (AMR)

AF:

0.00

AC:

AN:

39632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25472

East Asian (EAS)

AF:

0.00

AC:

AN:

36874

South Asian (SAS)

AF:

0.00

AC:

AN:

81648

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42342

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.00000458

AC:

AN:

1090572

Other (OTH)

AF:

0.00

AC:

AN:

58688

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.417

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000847

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.060

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.75

M_CAP

Uncertain

0.087

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.44

MutationAssessor

Benign

-1.1

PhyloP100

0.94

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.47

REVEL

Benign

0.27

Sift

Uncertain

0.020

Sift4G

Benign

0.21

Polyphen

0.70

Vest4

0.13

MutPred

0.53

Gain of disorder (P = 0.055)

MVP

0.74

MPC

0.94

ClinPred

0.15

GERP RS

2.5

PromoterAI

0.039

Neutral

(source)

Varity_R

0.16

gMVP

0.16

Mutation Taster

=87/13

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over