chr3-57296861-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001366028.2(DNAH12):​c.11518G>A​(p.Gly3840Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00004 in 1,551,270 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

DNAH12
NM_001366028.2 missense

Scores

2
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.09
Variant links:
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAH12NM_001366028.2 linkc.11518G>A p.Gly3840Arg missense_variant Exon 71 of 74 ENST00000495027.6 NP_001352957.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNAH12ENST00000495027.6 linkc.11518G>A p.Gly3840Arg missense_variant Exon 71 of 74 5 NM_001366028.2 ENSP00000418137.2 E9PG32

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152058
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000447
AC:
7
AN:
156696
Hom.:
0
AF XY:
0.0000482
AC XY:
4
AN XY:
82970
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000118
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000988
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000429
AC:
60
AN:
1399212
Hom.:
0
Cov.:
31
AF XY:
0.0000420
AC XY:
29
AN XY:
690092
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000318
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000436
Gnomad4 OTH exome
AF:
0.0000862
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152058
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74252
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000122
Hom.:
0
Bravo
AF:
0.0000264

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.8914G>A (p.G2972R) alteration is located in exon 56 (coding exon 55) of the DNAH12 gene. This alteration results from a G to A substitution at nucleotide position 8914, causing the glycine (G) at amino acid position 2972 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.68
BayesDel_addAF
Benign
-0.051
T
BayesDel_noAF
Benign
-0.11
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.038
T;T
Eigen
Uncertain
0.33
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.96
D;D
M_CAP
Benign
0.022
T
MetaRNN
Uncertain
0.44
T;T
MetaSVM
Benign
-0.46
T
MutationAssessor
Uncertain
2.3
.;M
PrimateAI
Uncertain
0.67
T
PROVEAN
Pathogenic
-4.5
.;D
REVEL
Benign
0.22
Sift
Benign
0.061
.;T
Polyphen
0.87
.;P
Vest4
0.58
MutPred
0.54
.;Gain of sheet (P = 0.039);
MVP
0.37
ClinPred
0.66
D
GERP RS
5.3
Varity_R
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1372580111; hg19: chr3-57330889; API