rs374560534
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_001277115.2(DNAH11):c.11924C>T(p.Ala3975Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,613,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 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_001277115.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNAH11 | NM_001277115.2 | c.11924C>T | p.Ala3975Val | missense_variant | 73/82 | ENST00000409508.8 | NP_001264044.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNAH11 | ENST00000409508.8 | c.11924C>T | p.Ala3975Val | missense_variant | 73/82 | 5 | NM_001277115.2 | ENSP00000475939 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152172Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000257 AC: 64AN: 249038Hom.: 0 AF XY: 0.000370 AC XY: 50AN XY: 135102
GnomAD4 exome AF: 0.000153 AC: 224AN: 1461652Hom.: 0 Cov.: 31 AF XY: 0.000226 AC XY: 164AN XY: 727100
GnomAD4 genome AF: 0.0000722 AC: 11AN: 152290Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5AN XY: 74466
ClinVar
Submissions by phenotype
DNAH11-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 01, 2023 | The DNAH11 c.11924C>T variant is predicted to result in the amino acid substitution p.Ala3975Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.21% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/7-21908566-C-T). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 01, 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 - |
Primary ciliary dyskinesia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 12, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at