17-78425388-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_173628.4(DNAH17):c.13099C>T(p.Pro4367Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000328 in 1,613,878 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P4367P) has been classified as Benign.
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
DNAH17
NM_173628.4 missense
NM_173628.4 missense
Scores
1
5
7
Clinical Significance
Conservation
PhyloP100: 6.64
Genes affected
DNAH17 (HGNC:2946): (dynein axonemal heavy chain 17) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. DNAH17 is a heavy chain associated with axonemal dynein (Milisav and Affara, 1998 [PubMed 9545504]).[supplied by OMIM, Mar 2008]
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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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH17 | NM_173628.4 | c.13099C>T | p.Pro4367Ser | missense_variant | 80/81 | ENST00000389840.7 | |
DNAH17 | XM_011525416.3 | c.13111C>T | p.Pro4371Ser | missense_variant | 80/81 | ||
DNAH17 | XM_024451013.2 | c.12967C>T | p.Pro4323Ser | missense_variant | 79/80 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH17 | ENST00000389840.7 | c.13099C>T | p.Pro4367Ser | missense_variant | 80/81 | 5 | NM_173628.4 | P1 | |
DNAH17 | ENST00000586052.5 | n.6260C>T | non_coding_transcript_exon_variant | 34/35 | 5 | ||||
DNAH17 | ENST00000590227.5 | n.2773C>T | non_coding_transcript_exon_variant | 12/13 | 2 | ||||
DNAH17 | ENST00000591369.5 | c.*30C>T | 3_prime_UTR_variant, NMD_transcript_variant | 27/28 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152200Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251116Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135720
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GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461678Hom.: 0 Cov.: 32 AF XY: 0.0000371 AC XY: 27AN XY: 727118
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74346
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 20, 2023 | The c.13099C>T (p.P4367S) alteration is located in exon 80 (coding exon 79) of the DNAH17 gene. This alteration results from a C to T substitution at nucleotide position 13099, causing the proline (P) at amino acid position 4367 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
Vest4
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at