rs11574115
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_000376.3(VDR):c.1085C>T(p.Thr362Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000271 in 1,614,050 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000376.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VDR | NM_000376.3 | c.1085C>T | p.Thr362Ile | missense_variant | 10/10 | ENST00000549336.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VDR | ENST00000549336.6 | c.1085C>T | p.Thr362Ile | missense_variant | 10/10 | 1 | NM_000376.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00153 AC: 233AN: 152124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000378 AC: 95AN: 251378Hom.: 1 AF XY: 0.000272 AC XY: 37AN XY: 135868
GnomAD4 exome AF: 0.000140 AC: 204AN: 1461808Hom.: 2 Cov.: 30 AF XY: 0.000135 AC XY: 98AN XY: 727218
GnomAD4 genome ? AF: 0.00153 AC: 233AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.00152 AC XY: 113AN XY: 74418
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 16, 2023 | Variant summary: VDR c.1085C>T (p.Thr362Ile) results in a non-conservative amino acid change located in the nuclear hormone receptor, ligand-binding domain (IPR000536) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00038 in 251378 control chromosomes, predominantly at a frequency of 0.0056 within the African or African-American subpopulation in the gnomAD database, including 1 homozygotes, suggesting it could be a benign polymorphism found primarily in individuals of African ancestry. To our knowledge, no occurrence of c.1085C>T in individuals affected with Vitamin D-Dependent Rickets Type II With Alopecia and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as benign, and one submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly benign. - |
Vitamin D-dependent rickets type II with alopecia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at