12-49089946-C-G
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_021044.4(DHH):āc.1104G>Cā(p.Ala368=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000019 in 1,579,170 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: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 7.0e-7 ( 0 hom. )
Consequence
DHH
NM_021044.4 synonymous
NM_021044.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.197
Genes affected
DHH (HGNC:2865): (desert hedgehog signaling molecule) This gene encodes a member of the hedgehog family. The hedgehog gene family encodes signaling molecules that play an important role in regulating morphogenesis. This protein is predicted to be made as a precursor that is autocatalytically cleaved; the N-terminal portion is soluble and contains the signalling activity while the C-terminal portion is involved in precursor processing. More importantly, the C-terminal product covalently attaches a cholesterol moiety to the N-terminal product, restricting the N-terminal product to the cell surface and preventing it from freely diffusing throughout the organism. Defects in this protein have been associated with partial gonadal dysgenesis (PGD) accompanied by minifascicular polyneuropathy. This protein may be involved in both male gonadal differentiation and perineurial development. [provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
Variant 12-49089946-C-G is Benign according to our data. Variant chr12-49089946-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3042896.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=0.197 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DHH | NM_021044.4 | c.1104G>C | p.Ala368= | synonymous_variant | 3/3 | ENST00000649637.2 | NP_066382.1 | |
DHH | XM_017019380.2 | c.963G>C | p.Ala321= | synonymous_variant | 3/3 | XP_016874869.1 | ||
DHH | XM_017019381.2 | c.762G>C | p.Ala254= | synonymous_variant | 3/3 | XP_016874870.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DHH | ENST00000649637.2 | c.1104G>C | p.Ala368= | synonymous_variant | 3/3 | NM_021044.4 | ENSP00000497483 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152240Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000536 AC: 1AN: 186418Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 101318
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GnomAD4 exome AF: 7.01e-7 AC: 1AN: 1426930Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 706740
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74376
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
DHH-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 11, 2019 | 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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Benign
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DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at