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12-123772914-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001372106.1(DNAH10):c.477C>T(p.Asn159=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000888 in 1,612,744 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0046 ( 5 hom., cov: 33)
Exomes 𝑓: 0.00050 ( 6 hom. )

Consequence

DNAH10
NM_001372106.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.30
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-123772914-C-T is Benign according to our data. Variant chr12-123772914-C-T is described in ClinVar as [Benign]. Clinvar id is 787937.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.3 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000505 (737/1460480) while in subpopulation AFR AF= 0.0166 (554/33418). AF 95% confidence interval is 0.0154. There are 6 homozygotes in gnomad4_exome. There are 318 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DNAH10NM_001372106.1 linkuse as main transcriptc.477C>T p.Asn159= synonymous_variant 4/79 ENST00000673944.1
LOC105370044XR_945481.4 linkuse as main transcriptn.496-7666G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DNAH10ENST00000673944.1 linkuse as main transcriptc.477C>T p.Asn159= synonymous_variant 4/79 NM_001372106.1 P1
DNAH10ENST00000409039.8 linkuse as main transcriptc.477C>T p.Asn159= synonymous_variant 4/785
DNAH10ENST00000638045.1 linkuse as main transcriptc.294C>T p.Asn98= synonymous_variant 4/785 Q8IVF4-1
DNAH10ENST00000614082.1 linkuse as main transcriptc.-253C>T 5_prime_UTR_variant 4/205

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00457
AC:
695
AN:
152146
Hom.:
5
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0158
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00177
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00382
GnomAD3 exomes
AF:
0.00108
AC:
268
AN:
248332
Hom.:
3
AF XY:
0.000824
AC XY:
111
AN XY:
134780
show subpopulations
Gnomad AFR exome
AF:
0.0152
Gnomad AMR exome
AF:
0.000585
Gnomad ASJ exome
AF:
0.0000996
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000329
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000355
Gnomad OTH exome
AF:
0.00117
GnomAD4 exome
AF:
0.000505
AC:
737
AN:
1460480
Hom.:
6
Cov.:
30
AF XY:
0.000438
AC XY:
318
AN XY:
726552
show subpopulations
Gnomad4 AFR exome
AF:
0.0166
Gnomad4 AMR exome
AF:
0.000989
Gnomad4 ASJ exome
AF:
0.000115
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000581
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000342
Gnomad4 OTH exome
AF:
0.00148
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00456
AC:
695
AN:
152264
Hom.:
5
Cov.:
33
AF XY:
0.00436
AC XY:
325
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.0158
Gnomad4 AMR
AF:
0.00176
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00378
Alfa
AF:
0.00202
Hom.:
3
Bravo
AF:
0.00549
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.0000547
EpiControl
AF:
0.000178

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 08, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
Cadd
Benign
0.19
Dann
Benign
0.43

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: rs147457213; hg19: chr12-124257461; API