3-57293819-T-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001366028.2(DNAH12):āc.11845A>Gā(p.Lys3949Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000677 in 1,551,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00036 ( 0 hom., cov: 31)
Exomes š: 0.000036 ( 0 hom. )
Consequence
DNAH12
NM_001366028.2 missense
NM_001366028.2 missense
Scores
2
7
5
Clinical Significance
Conservation
PhyloP100: 7.96
Genes affected
DNAH12 (HGNC:2943): (dynein axonemal heavy chain 12) Predicted to enable several functions, including ATP binding activity; dynein intermediate chain binding activity; and dynein light intermediate chain binding activity. Predicted to be involved in microtubule-based movement. Predicted to be located in cilium; cytoplasm; and microtubule. Predicted to be part of dynein complex. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17174089).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH12 | NM_001366028.2 | c.11845A>G | p.Lys3949Glu | missense_variant | 74/74 | ENST00000495027.6 | |
LOC124909384 | XR_007095923.1 | n.602+427T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH12 | ENST00000495027.6 | c.11845A>G | p.Lys3949Glu | missense_variant | 74/74 | 5 | NM_001366028.2 | P1 | |
ENST00000656348.1 | n.310+427T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.000362 AC: 55AN: 152012Hom.: 0 Cov.: 31
GnomAD3 genomes
AF:
AC:
55
AN:
152012
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000701 AC: 11AN: 156830Hom.: 0 AF XY: 0.0000724 AC XY: 6AN XY: 82874
GnomAD3 exomes
AF:
AC:
11
AN:
156830
Hom.:
AF XY:
AC XY:
6
AN XY:
82874
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000357 AC: 50AN: 1399230Hom.: 0 Cov.: 34 AF XY: 0.0000290 AC XY: 20AN XY: 690094
GnomAD4 exome
AF:
AC:
50
AN:
1399230
Hom.:
Cov.:
34
AF XY:
AC XY:
20
AN XY:
690094
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000362 AC: 55AN: 152012Hom.: 0 Cov.: 31 AF XY: 0.000377 AC XY: 28AN XY: 74268
GnomAD4 genome
AF:
AC:
55
AN:
152012
Hom.:
Cov.:
31
AF XY:
AC XY:
28
AN XY:
74268
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
1
ESP6500EA
AF:
AC:
0
ExAC
AF:
AC:
2
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 06, 2024 | The c.9241A>G (p.K3081E) alteration is located in exon 59 (coding exon 58) of the DNAH12 gene. This alteration results from a A to G substitution at nucleotide position 9241, causing the lysine (K) at amino acid position 3081 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
T
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
Polyphen
0.97
.;D
Vest4
MVP
ClinPred
T
GERP RS
Varity_R
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at