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GeneBe

12-123918806-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_001372106.1(DNAH10):​c.11363C>T​(p.Ser3788Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000623 in 1,613,802 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00065 ( 2 hom. )

Consequence

DNAH10
NM_001372106.1 missense

Scores

4
10

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 3.65
Variant links:
Genes affected
DNAH10 (HGNC:2941): (dynein axonemal heavy chain 10) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. The axonemal dyneins, found in cilia and flagella, are components of the outer and inner dynein arms attached to the peripheral microtubule doublets. DNAH10 is an inner arm dynein heavy chain (Maiti et al., 2000 [PubMed 11175280]).[supplied by OMIM, Mar 2008]
CCDC92 (HGNC:29563): (coiled-coil domain containing 92) Enables identical protein binding activity. Located in centriole; centrosome; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2
Missense variant where missense usually causes diseases, DNAH10
BP4
Computational evidence support a benign effect (MetaRNN=0.08204827).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DNAH10NM_001372106.1 linkuse as main transcriptc.11363C>T p.Ser3788Phe missense_variant 65/79 ENST00000673944.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DNAH10ENST00000673944.1 linkuse as main transcriptc.11363C>T p.Ser3788Phe missense_variant 65/79 NM_001372106.1 P1
DNAH10ENST00000409039.8 linkuse as main transcriptc.11192C>T p.Ser3731Phe missense_variant 64/785
DNAH10ENST00000638045.1 linkuse as main transcriptc.11009C>T p.Ser3670Phe missense_variant 64/785 Q8IVF4-1
CCDC92ENST00000542348.5 linkuse as main transcriptn.408G>A non_coding_transcript_exon_variant 3/34

Frequencies

GnomAD3 genomes
AF:
0.000329
AC:
50
AN:
152190
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000661
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000397
AC:
99
AN:
249110
Hom.:
0
AF XY:
0.000377
AC XY:
51
AN XY:
135166
show subpopulations
Gnomad AFR exome
AF:
0.000129
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000232
Gnomad NFE exome
AF:
0.000779
Gnomad OTH exome
AF:
0.000496
GnomAD4 exome
AF:
0.000654
AC:
956
AN:
1461612
Hom.:
2
Cov.:
31
AF XY:
0.000609
AC XY:
443
AN XY:
727078
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000187
Gnomad4 NFE exome
AF:
0.000807
Gnomad4 OTH exome
AF:
0.000762
GnomAD4 genome
AF:
0.000329
AC:
50
AN:
152190
Hom.:
0
Cov.:
33
AF XY:
0.000296
AC XY:
22
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000661
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000580
Hom.:
0
Bravo
AF:
0.000359
TwinsUK
AF:
0.00135
AC:
5
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.00131
AC:
11
ExAC
AF:
0.000529
AC:
64
EpiCase
AF:
0.000382
EpiControl
AF:
0.000889

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 07, 2022The c.11009C>T (p.S3670F) alteration is located in exon 64 (coding exon 64) of the DNAH10 gene. This alteration results from a C to T substitution at nucleotide position 11009, causing the serine (S) at amino acid position 3670 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenNov 01, 2023DNAH10: PM2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
23
DANN
Uncertain
0.98
Eigen
Benign
0.082
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Benign
0.0045
T
MetaRNN
Benign
0.082
T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.32
T
REVEL
Benign
0.072
Polyphen
0.0030
.;B
MVP
0.21
MPC
0.16
ClinPred
0.040
T
GERP RS
4.9
Varity_R
0.18
gMVP
0.39

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs200033987; hg19: chr12-124403353; COSMIC: COSV105936494; COSMIC: COSV105936494; API