7-21620041-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001277115.2(DNAH11):c.4463C>T(p.Ser1488Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000217 in 1,605,864 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict 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. S1488S) has been classified as Benign.
Frequency
Consequence
NM_001277115.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH11 | NM_001277115.2 | c.4463C>T | p.Ser1488Phe | missense_variant | 25/82 | ENST00000409508.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH11 | ENST00000409508.8 | c.4463C>T | p.Ser1488Phe | missense_variant | 25/82 | 5 | NM_001277115.2 | P1 | |
DNAH11 | ENST00000465593.1 | n.489C>T | non_coding_transcript_exon_variant | 3/4 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00120 AC: 182AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000263 AC: 64AN: 243032Hom.: 0 AF XY: 0.000220 AC XY: 29AN XY: 131660
GnomAD4 exome AF: 0.000115 AC: 167AN: 1453600Hom.: 2 Cov.: 30 AF XY: 0.0000997 AC XY: 72AN XY: 722342
GnomAD4 genome AF: 0.00120 AC: 182AN: 152264Hom.: 0 Cov.: 32 AF XY: 0.00105 AC XY: 78AN XY: 74442
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 17, 2018 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 25, 2024 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
DNAH11-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 25, 2023 | 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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at