17-49973224-C-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2
The NM_138281.3(DLX4):c.435C>T(p.Pro145Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,614,012 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 Likely benign (no stars).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
DLX4
NM_138281.3 synonymous
NM_138281.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.59
Genes affected
DLX4 (HGNC:2917): (distal-less homeobox 4) Many vertebrate homeo box-containing genes have been identified on the basis of their sequence similarity with Drosophila developmental genes. Members of the Dlx gene family contain a homeobox that is related to that of Distal-less (Dll), a gene expressed in the head and limbs of the developing fruit fly. The Distal-less (Dlx) family of genes comprises at least 6 different members, DLX1-DLX6. The DLX proteins are postulated to play a role in forebrain and craniofacial development. Three transcript variants have been described for this gene, however, the full length nature of one variant has not been described. Studies of the two splice variants revealed that one encoded isoform functions as a repressor of the beta-globin gene while the other isoform lacks that function. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.3).
BP6
Variant 17-49973224-C-T is Benign according to our data. Variant chr17-49973224-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3054114.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=-1.59 with no splicing effect.
BS2
High AC in GnomAd4 at 16 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DLX4 | NM_138281.3 | c.435C>T | p.Pro145Pro | synonymous_variant | 2/3 | ENST00000240306.5 | NP_612138.1 | |
DLX4 | NM_001934.4 | c.219C>T | p.Pro73Pro | synonymous_variant | 1/2 | NP_001925.2 | ||
DLX4 | XM_047435517.1 | c.219C>T | p.Pro73Pro | synonymous_variant | 2/3 | XP_047291473.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152230Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000440 AC: 11AN: 249878Hom.: 0 AF XY: 0.0000517 AC XY: 7AN XY: 135406
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GnomAD4 exome AF: 0.000106 AC: 155AN: 1461782Hom.: 0 Cov.: 31 AF XY: 0.0000976 AC XY: 71AN XY: 727204
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GnomAD4 genome AF: 0.000105 AC: 16AN: 152230Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74368
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
DLX4-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 07, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at