chr11-71435593-G-T
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PM5PP3_StrongPP5
The NM_001360.3(DHCR7):c.1210C>A(p.Arg404Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000618 in 1,457,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R404G) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001360.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DHCR7 | NM_001360.3 | c.1210C>A | p.Arg404Ser | missense_variant | 9/9 | ENST00000355527.8 | |
DHCR7 | NM_001163817.2 | c.1210C>A | p.Arg404Ser | missense_variant | 9/9 | ||
DHCR7 | XM_011544777.3 | c.1344C>A | p.Pro448= | synonymous_variant | 9/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DHCR7 | ENST00000355527.8 | c.1210C>A | p.Arg404Ser | missense_variant | 9/9 | 1 | NM_001360.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 35
GnomAD3 exomes AF: 0.00000414 AC: 1AN: 241396Hom.: 0 AF XY: 0.00000756 AC XY: 1AN XY: 132196
GnomAD4 exome AF: 0.00000618 AC: 9AN: 1457350Hom.: 0 Cov.: 84 AF XY: 0.00000689 AC XY: 5AN XY: 725180
GnomAD4 genome Cov.: 35
ClinVar
Submissions by phenotype
Smith-Lemli-Opitz syndrome Pathogenic:1Uncertain:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 01, 2022 | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DHCR7 protein function. ClinVar contains an entry for this variant (Variation ID: 552797). This missense change has been observed in individual(s) with clinical features of DHCR7-related conditions (PMID: 10677299, 10814720, 33578785). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 404 of the DHCR7 protein (p.Arg404Ser). This variant disrupts the p.Arg404 amino acid residue in DHCR7. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9653161, 10677299, 12818773, 15896653). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jul 07, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at