Variant 17-48550624-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001384749.1(HOXB3):c.1006G>A(p.Ala336Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000438 in 1,370,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000044 ( 0 hom. )

Consequence

HOXB3
NM_001384749.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.83

Variant links:

Genes affected

HOXB3 (HGNC:5114): (homeobox B3) 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 development. Increased expression of this gene is associated with a distinct biologic subset of acute myeloid leukemia (AML). [provided by RefSeq, Jul 2008]

HOXB3 links:

HOXB-AS1 (HGNC:43744): (HOXB cluster antisense RNA 1)

HOXB-AS1 links:

HOXB-AS3 (HGNC:40283): (HOXB cluster antisense RNA 3)

HOXB-AS3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21171433).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXB3	NM_001384749.1 linkuse as main transcript	c.1006G>A	p.Ala336Thr	missense_variant	5/5	ENST00000498678.6	NP_001371678.1
HOXB-AS1	NR_102279.1 linkuse as main transcript	n.579+222C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXB3	ENST00000498678.6 linkuse as main transcript	c.1006G>A	p.Ala336Thr	missense_variant	5/5	2	NM_001384749.1	ENSP00000420595	P1	P14651-1
HOXB-AS1	ENST00000435312.5 linkuse as main transcript	n.579+222C>T		intron_variant, non_coding_transcript_variant		5
HOXB-AS3	ENST00000465846.6 linkuse as main transcript	n.77+678C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000229

AC:

AN:

174822

Hom.:

AF XY:

0.00

AC XY:

AN XY:

93222

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000185

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000438

AC:

AN:

1370188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

672906

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

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:

0.00000187

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000333

AC:

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

Aug 30, 2022

The c.1006G>A (p.A336T) alteration is located in exon 4 (coding exon 2) of the HOXB3 gene. This alteration results from a G to A substitution at nucleotide position 1006, causing the alanine (A) at amino acid position 336 to be replaced by a threonine (T). 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

-0.26

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

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

Eigen

Benign

-0.036

Eigen_PC

Benign

-0.035

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.79

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

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.21

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

MetaSVM

Uncertain

0.15

MutationAssessor

Benign

0.69

N;.;N;N;.;.;.;N

MutationTaster

Benign

0.96

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

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.8

N;N;N;N;N;N;N;N

REVEL

Uncertain

0.33

Sift

Uncertain

0.011

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

Sift4G

Benign

0.13

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

Polyphen

0.63

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

Vest4

0.097

MutPred

0.15

Gain of glycosylation at A336 (P = 0.0079);.;Gain of glycosylation at A336 (P = 0.0079);Gain of glycosylation at A336 (P = 0.0079);.;.;.;Gain of glycosylation at A336 (P = 0.0079);

MVP

0.77

MPC

0.42

ClinPred

0.13

GERP RS

1.8

Varity_R

0.14

gMVP

0.39

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