3-57296872-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001366028.2(DNAH12):āc.11507T>Cā(p.Ile3836Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000773 in 1,551,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I3836V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001366028.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH12 | NM_001366028.2 | c.11507T>C | p.Ile3836Thr | missense_variant | 71/74 | ENST00000495027.6 | |
LOC124909384 | XR_007095923.1 | n.603-1154A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH12 | ENST00000495027.6 | c.11507T>C | p.Ile3836Thr | missense_variant | 71/74 | 5 | NM_001366028.2 | P1 | |
ENST00000656348.1 | n.311-1154A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000128 AC: 2AN: 156760Hom.: 0 AF XY: 0.0000120 AC XY: 1AN XY: 83018
GnomAD4 exome AF: 0.00000786 AC: 11AN: 1399330Hom.: 0 Cov.: 31 AF XY: 0.0000130 AC XY: 9AN XY: 690162
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74358
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 16, 2021 | The c.8903T>C (p.I2968T) alteration is located in exon 56 (coding exon 55) of the DNAH12 gene. This alteration results from a T to C substitution at nucleotide position 8903, causing the isoleucine (I) at amino acid position 2968 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at