rs200798994
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_001369.3(DNAH5):c.11694G>T(p.Leu3898Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000886 in 1,614,084 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign 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. L3898L) has been classified as Likely benign.
Frequency
Consequence
NM_001369.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.11694G>T | p.Leu3898Phe | missense_variant | 68/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.11694G>T | p.Leu3898Phe | missense_variant | 68/79 | 1 | NM_001369.3 | P4 | |
DNAH5 | ENST00000681290.1 | c.11649G>T | p.Leu3883Phe | missense_variant | 68/79 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152130Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000915 AC: 23AN: 251258Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135792
GnomAD4 exome AF: 0.0000937 AC: 137AN: 1461836Hom.: 1 Cov.: 32 AF XY: 0.0000866 AC XY: 63AN XY: 727224
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152248Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74428
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 13, 2017 | The p.L3898F variant (also known as c.11694G>T), located in coding exon 68 of the DNAH5 gene, results from a G to T substitution at nucleotide position 11694. The leucine at codon 3898 is replaced by phenylalanine, an amino acid with highly similar 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. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Aug 03, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Primary ciliary dyskinesia 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at