17-48610570-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004502.4(HOXB7):​c.349G>T​(p.Asp117Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 34)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

HOXB7
NM_004502.4 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.39
Variant links:
Genes affected
HOXB7 (HGNC:5118): (homeobox B7) This gene is a member of the Antp homeobox family and encodes a protein with a homeobox DNA-binding domain. It is included in a cluster of homeobox B genes located on chromosome 17. The encoded nuclear protein functions as a sequence-specific transcription factor that is involved in cell proliferation and differentiation. Increased expression of this gene is associated with some cases of melanoma and ovarian carcinoma. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.35720402).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HOXB7NM_004502.4 linkc.349G>T p.Asp117Tyr missense_variant Exon 1 of 2 ENST00000239165.9 NP_004493.3 P09629

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HOXB7ENST00000239165.9 linkc.349G>T p.Asp117Tyr missense_variant Exon 1 of 2 1 NM_004502.4 ENSP00000239165.7 P09629
HOXB7ENST00000567101.2 linkn.60-2475G>T intron_variant Intron 1 of 1 2

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1385486
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
682206
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.:
34

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.349G>T (p.D117Y) alteration is located in exon 1 (coding exon 1) of the HOXB7 gene. This alteration results from a G to T substitution at nucleotide position 349, causing the aspartic acid (D) at amino acid position 117 to be replaced by a tyrosine (Y). 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
0.24
BayesDel_addAF
Uncertain
0.091
D
BayesDel_noAF
Benign
-0.11
CADD
Uncertain
25
DANN
Uncertain
0.98
DEOGEN2
Benign
0.35
T
Eigen
Benign
0.099
Eigen_PC
Benign
0.15
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.84
T
M_CAP
Uncertain
0.15
D
MetaRNN
Benign
0.36
T
MetaSVM
Uncertain
0.28
D
MutationAssessor
Benign
2.0
M
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
-1.5
N
REVEL
Uncertain
0.48
Sift
Benign
0.11
T
Sift4G
Uncertain
0.042
D
Polyphen
0.53
P
Vest4
0.42
MutPred
0.49
Gain of phosphorylation at D117 (P = 0.0166);
MVP
0.92
MPC
0.95
ClinPred
0.68
D
GERP RS
3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.21
gMVP
0.58

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.

Other links and lift over

hg19: chr17-46687932; API