rs201077964
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_001369.3(DNAH5):c.962C>T(p.Ser321Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000486 in 1,613,656 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). Synonymous variant affecting the same amino acid position (i.e. S321S) has been classified as Likely benign.
Frequency
Consequence
NM_001369.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000375 AC: 57AN: 152012Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.000315 AC: 79AN: 251036 AF XY: 0.000339 show subpopulations
GnomAD4 exome AF: 0.000498 AC: 728AN: 1461644Hom.: 0 Cov.: 32 AF XY: 0.000488 AC XY: 355AN XY: 727126 show subpopulations
GnomAD4 genome AF: 0.000375 AC: 57AN: 152012Hom.: 0 Cov.: 32 AF XY: 0.000350 AC XY: 26AN XY: 74226 show subpopulations
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 3 Pathogenic:1Uncertain:2
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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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
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Primary ciliary dyskinesia Uncertain:2Benign:1
The p.S321L variant (also known as c.962C>T), located in coding exon 7 of the DNAH5 gene, results from a C to T substitution at nucleotide position 962. The serine at codon 321 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
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not provided Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at