chr1-46510466-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_172225.2(DMBX1):c.155-10A>T variant causes a splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.0000031 in 1,612,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
DMBX1
NM_172225.2 splice_polypyrimidine_tract, intron
NM_172225.2 splice_polypyrimidine_tract, intron
Scores
1
2
16
Clinical Significance
Conservation
PhyloP100: 5.85
Genes affected
DMBX1 (HGNC:19026): (diencephalon/mesencephalon homeobox 1) This gene encodes a member of the bicoid sub-family of homeodomain-containing transcription factors. The encoded protein acts as a transcription factor and may play a role in brain and sensory organ development. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.24889782).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DMBX1 | NM_172225.2 | c.155-10A>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000360032.4 | |||
DMBX1 | NM_001387776.1 | c.160A>T | p.Thr54Ser | missense_variant | 3/5 | ||
DMBX1 | NM_147192.4 | c.160A>T | p.Thr54Ser | missense_variant | 4/6 | ||
DMBX1 | NM_001387775.1 | c.155-10A>T | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DMBX1 | ENST00000360032.4 | c.155-10A>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_172225.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152222Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460748Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726648
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74372
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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 10, 2022 | The c.160A>T (p.T54S) alteration is located in exon 2 (coding exon 2) of the DMBX1 gene. This alteration results from a A to T substitution at nucleotide position 160, causing the threonine (T) at amino acid position 54 to be replaced by a serine (S). 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
Uncertain
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of MoRF binding (P = 0.166);
MVP
ClinPred
T
GERP RS
Varity_R
Splicing
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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