Variant 17-48550545-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001384749.1(HOXB3):c.1085T>G(p.Leu362Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HOXB3
NM_001384749.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.05

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 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
HOXB3	NM_001384749.1 linkuse as main transcript	c.1085T>G	p.Leu362Arg	missense_variant	5/5	ENST00000498678.6	NP_001371678.1
HOXB-AS1	NR_102279.1 linkuse as main transcript	n.579+143A>C		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.1085T>G	p.Leu362Arg	missense_variant	5/5	2	NM_001384749.1	ENSP00000420595	P1	P14651-1
HOXB-AS1	ENST00000435312.5 linkuse as main transcript	n.579+143A>C		intron_variant, non_coding_transcript_variant		5
HOXB-AS3	ENST00000465846.6 linkuse as main transcript	n.77+599A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1376848

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

680260

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.:

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 12, 2021

The c.1085T>G (p.L362R) alteration is located in exon 4 (coding exon 2) of the HOXB3 gene. This alteration results from a T to G substitution at nucleotide position 1085, causing the leucine (L) at amino acid position 362 to be replaced by an arginine (R). 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

Uncertain

0.42

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.59

D;.;D;D;T;.;.;D

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.78

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

M_CAP

Pathogenic

0.67

MetaRNN

Uncertain

0.53

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

MetaSVM

Uncertain

0.35

MutationAssessor

Benign

1.4

L;.;L;L;.;.;.;L

MutationTaster

Benign

0.99

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

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-3.3

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

REVEL

Uncertain

0.58

Sift

Pathogenic

0.0

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

Sift4G

Uncertain

0.0070

D;D;D;D;T;T;D;D

Polyphen

0.97

D;.;D;D;.;.;.;D

Vest4

0.45

MutPred

0.19

Gain of methylation at L362 (P = 0.0329);.;Gain of methylation at L362 (P = 0.0329);Gain of methylation at L362 (P = 0.0329);.;.;.;Gain of methylation at L362 (P = 0.0329);

MVP

0.77

MPC

1.4

ClinPred

0.99

GERP RS

3.2

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.8

Varity_R

0.80

gMVP

0.71

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over