Variant chr17-48593589-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002147.4(HOXB5):c.94G>T(p.Gly32Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,460,782 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

HOXB5
NM_002147.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.86

Variant links:

Genes affected

HOXB5 (HGNC:5116): (homeobox B5) This gene is a member of the Antp homeobox family and encodes a nuclear protein with a homeobox DNA-binding domain. It is included in a cluster of homeobox B genes located on chromosome 17. The encoded protein functions as a sequence-specific transcription factor that is involved in lung and gut development. Increased expression of this gene is associated with a distinct biologic subset of acute myeloid leukemia (AML) and the occurrence of bronchopulmonary sequestration (BPS) and congenital cystic adenomatoid malformation (CCAM) tissue. [provided by RefSeq, Jul 2008]

HOXB5 links:

HOXB-AS3 (HGNC:):

HOXB-AS3 links:

Genome browser will be placed here

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
HOXB5	NM_002147.4 linkuse as main transcript	c.94G>T	p.Gly32Cys	missense_variant	1/2	ENST00000239151.6	NP_002138.1	P09067

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXB5	ENST00000239151.6 linkuse as main transcript	c.94G>T	p.Gly32Cys	missense_variant	1/2	1	NM_002147.4	ENSP00000239151.4		P09067

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000817

AC:

AN:

244844

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

133910

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:

0.0000183

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460782

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726708

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Apr 08, 2024

The c.94G>T (p.G32C) alteration is located in exon 1 (coding exon 1) of the HOXB5 gene. This alteration results from a G to T substitution at nucleotide position 94, causing the glycine (G) at amino acid position 32 to be replaced by a cysteine (C). 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

0.29

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.21

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.64

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.63

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.48

MetaSVM

Pathogenic

0.89

MutationAssessor

Uncertain

2.5

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-3.4

REVEL

Pathogenic

0.74

Sift

Benign

0.053

Sift4G

Benign

0.067

Polyphen

1.0

Vest4

0.29

MutPred

0.33

Loss of glycosylation at S31 (P = 0.0225);

MVP

1.0

MPC

1.6

ClinPred

0.99

GERP RS

5.4

Varity_R

0.44

gMVP

0.72

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over