6-38945559-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BS1_SupportingBS2
The NM_001206927.2(DNAH8):c.12100C>T(p.Leu4034Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,614,136 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001206927.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.12100C>T | p.Leu4034Phe | missense_variant | Exon 80 of 93 | ENST00000327475.11 | NP_001193856.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNAH8 | ENST00000327475.11 | c.12100C>T | p.Leu4034Phe | missense_variant | Exon 80 of 93 | 5 | NM_001206927.2 | ENSP00000333363.7 | ||
DNAH8 | ENST00000359357.7 | c.11449C>T | p.Leu3817Phe | missense_variant | Exon 78 of 91 | 2 | ENSP00000352312.3 | |||
DNAH8 | ENST00000449981.6 | c.12100C>T | p.Leu4034Phe | missense_variant | Exon 79 of 82 | 5 | ENSP00000415331.2 | |||
DNAH8-AS1 | ENST00000416948.1 | n.52+7489G>A | intron_variant | Intron 1 of 3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000835 AC: 127AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000919 AC: 231AN: 251434Hom.: 0 AF XY: 0.000868 AC XY: 118AN XY: 135884
GnomAD4 exome AF: 0.00127 AC: 1853AN: 1461840Hom.: 3 Cov.: 31 AF XY: 0.00129 AC XY: 935AN XY: 727220
GnomAD4 genome AF: 0.000834 AC: 127AN: 152296Hom.: 0 Cov.: 32 AF XY: 0.000806 AC XY: 60AN XY: 74460
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2Benign:1
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not specified Uncertain:1
The c.12100C>T (p.L4034F) alteration is located in exon 80 (coding exon 79) of the DNAH8 gene. This alteration results from a C to T substitution at nucleotide position 12100, causing the leucine (L) at amino acid position 4034 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
DNAH8-related disorder Uncertain:1
The DNAH8 c.12100C>T variant is predicted to result in the amino acid substitution p.Leu4034Phe. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.18% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant has interpretations of likely benign (1) uncertain significance (4) in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/525268/). 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
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at