17-48550756-G-C

Variant names:

• chr17-48550756-G-C
• rs747283545
• NM_001384749.1:c.874C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001384749.1(HOXB3):​c.874C>G​(p.Pro292Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. P292R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HOXB3 NM_001384749.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.55
• Publications: 0 publications found

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]

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

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384749.1. 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
	HOXB3	NM_001384749.1	MANE Select	c.874C>G	p.Pro292Ala	missense	Exon 5 of 5	NP_001371678.1	P14651-1
	HOXB3	NM_001384747.1		c.874C>G	p.Pro292Ala	missense	Exon 3 of 3	NP_001371676.1	P14651-1
	HOXB3	NM_002146.4		c.874C>G	p.Pro292Ala	missense	Exon 4 of 4	NP_002137.4	B3KNJ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXB3	ENST00000498678.6	TSL:2 MANE Select	c.874C>G	p.Pro292Ala	missense	Exon 5 of 5	ENSP00000420595.1	P14651-1
	HOXB3	ENST00000311626.8	TSL:1	c.874C>G	p.Pro292Ala	missense	Exon 4 of 4	ENSP00000308252.4	P14651-1
	HOXB3	ENST00000470495.1	TSL:1	c.874C>G	p.Pro292Ala	missense	Exon 2 of 2	ENSP00000417207.1	P14651-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.67	D
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Uncertain	0.65	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.5
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Uncertain	0.52
Sift	Uncertain	0.029	D
Sift4G	Benign	0.092	T
Polyphen		1.0	D
Vest4		0.49
MutPred		0.14		Loss of glycosylation at P292 (P = 0.0335)
MVP		0.74
MPC		1.0
ClinPred		0.98	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.39
gMVP		0.60

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

Other links and lift over

dbSNP: rs747283545; hg19: chr17-46628118;