rs375218798
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_001369.3(DNAH5):c.3064G>A(p.Val1022Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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_001369.3 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 | UniProt |
---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.3064G>A | p.Val1022Ile | missense_variant | 20/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.3064G>A | p.Val1022Ile | missense_variant | 20/79 | 1 | NM_001369.3 | P4 | |
ENST00000503244.2 | n.254-13575C>T | intron_variant, non_coding_transcript_variant | 4 | ||||||
DNAH5 | ENST00000681290.1 | c.3019G>A | p.Val1007Ile | missense_variant | 20/79 | A1 | |||
ENST00000637153.1 | n.214-13575C>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152100Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251214Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135752
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461870Hom.: 0 Cov.: 34 AF XY: 0.0000165 AC XY: 12AN XY: 727242
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74426
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1Benign:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 07, 2023 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 27, 2024 | Variant summary: DNAH5 c.3064G>A (p.Val1022Ile) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 251214 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3064G>A in individuals affected with Primary ciliary dyskinesia 3 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 407235). Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at