chr17-48550813-C-T

Variant names:

• chr17-48550813-C-T
• NM_001384749.1:c.817G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001384749.1(HOXB3):​c.817G>A​(p.Ala273Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HOXB3 NM_001384749.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.44
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25952452).

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.817G>A	p.Ala273Thr	missense	Exon 5 of 5	NP_001371678.1	P14651-1
	HOXB3	NM_001384747.1		c.817G>A	p.Ala273Thr	missense	Exon 3 of 3	NP_001371676.1	P14651-1
	HOXB3	NM_002146.4		c.817G>A	p.Ala273Thr	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.817G>A	p.Ala273Thr	missense	Exon 5 of 5	ENSP00000420595.1	P14651-1
	HOXB3	ENST00000311626.8	TSL:1	c.817G>A	p.Ala273Thr	missense	Exon 4 of 4	ENSP00000308252.4	P14651-1
	HOXB3	ENST00000470495.1	TSL:1	c.817G>A	p.Ala273Thr	missense	Exon 2 of 2	ENSP00000417207.1	P14651-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.51	D
Eigen	Benign	0.015
Eigen_PC	Benign	0.059
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	1.5	L
PhyloP100		5.4
PrimateAI	Uncertain	0.79	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.34
Sift	Benign	0.079	T
Sift4G	Benign	0.25	T
Polyphen		0.46	P
Vest4		0.16
MutPred		0.15		Gain of glycosylation at A273 (P = 0.0093)
MVP		0.77
MPC		0.52
ClinPred		0.80	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.23
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

Other links and lift over

hg19: chr17-46628175;