chr17-48614482-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_024016.4(HOXB8):c.223G>A(p.Ala75Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,728 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
HOXB8
NM_024016.4 missense
NM_024016.4 missense
Scores
2
7
10
Clinical Significance
Conservation
PhyloP100: 5.83
Genes affected
HOXB8 (HGNC:5119): (homeobox B8) 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 colorectal cancer. Mice that have had the murine ortholog of this gene knocked out exhibit an excessive pathologic grooming behavior. This behavior is similar to the behavior of humans suffering from the obsessive-compulsive spectrum disorder trichotillomania. [provided by RefSeq, Jul 2008]
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]
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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 | UniProt |
---|---|---|---|---|---|---|---|
HOXB8 | NM_024016.4 | c.223G>A | p.Ala75Thr | missense_variant | 1/2 | ENST00000239144.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HOXB8 | ENST00000239144.5 | c.223G>A | p.Ala75Thr | missense_variant | 1/2 | 2 | NM_024016.4 | P4 | |
HOXB8 | ENST00000576562.1 | c.223G>A | p.Ala75Thr | missense_variant | 1/2 | 2 | A1 | ||
HOXB7 | ENST00000567101.2 | n.60-6387G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
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31
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250712Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135730
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461728Hom.: 0 Cov.: 38 AF XY: 0.00000138 AC XY: 1AN XY: 727192
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GnomAD4 genome Cov.: 31
GnomAD4 genome
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31
ExAC
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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 | Nov 09, 2021 | The c.223G>A (p.A75T) alteration is located in exon 1 (coding exon 1) of the HOXB8 gene. This alteration results from a G to A substitution at nucleotide position 223, causing the alanine (A) at amino acid position 75 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Gain of glycosylation at A75 (P = 0.0158);Gain of glycosylation at A75 (P = 0.0158);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at