Variant chr12-123928381-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001372106.1(DNAH10):c.12106-6G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 1,584,148 control chromosomes in the GnomAD database, including 183 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0098 ( 13 hom., cov: 32)

Exomes 𝑓: 0.014 ( 170 hom. )

Consequence

DNAH10
NM_001372106.1 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00009248

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.05

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]

DNAH10 links:

DNAH10OS (HGNC:37121): (dynein axonemal heavy chain 10 opposite strand)

DNAH10OS links:

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]

CCDC92 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 12-123928381-G-A is Benign according to our data. Variant chr12-123928381-G-A is described in ClinVar as [Benign]. Clinvar id is 2643539.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-123928381-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.014 (20039/1431874) while in subpopulation NFE AF= 0.0164 (17985/1097768). AF 95% confidence interval is 0.0162. There are 170 homozygotes in gnomad4_exome. There are 9789 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH10	NM_001372106.1 linkuse as main transcript	c.12106-6G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000673944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH10	ENST00000673944.1 linkuse as main transcript	c.12106-6G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_001372106.1	P1
DNAH10OS	ENST00000514254.3 linkuse as main transcript	n.3083C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00982

AC:

1494

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00357

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.0127

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00518

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0146

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00998

AC:

2004

AN:

200778

Hom.:

AF XY:

0.00994

AC XY:

1082

AN XY:

108840

show subpopulations

Gnomad AFR exome

AF:

0.00224

Gnomad AMR exome

AF:

0.0101

Gnomad ASJ exome

AF:

0.0126

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00222

Gnomad FIN exome

AF:

0.00570

Gnomad NFE exome

AF:

0.0152

Gnomad OTH exome

AF:

0.0162

GnomAD4 exome

AF:

0.0140

AC:

20039

AN:

1431874

Hom.:

170

Cov.:

AF XY:

0.0138

AC XY:

9789

AN XY:

709520

show subpopulations

Gnomad4 AFR exome

AF:

0.00212

Gnomad4 AMR exome

AF:

0.00932

Gnomad4 ASJ exome

AF:

0.0113

Gnomad4 EAS exome

AF:

0.0000522

Gnomad4 SAS exome

AF:

0.00228

Gnomad4 FIN exome

AF:

0.00631

Gnomad4 NFE exome

AF:

0.0164

Gnomad4 OTH exome

AF:

0.0131

GnomAD4 genome

AF:

0.00981

AC:

1494

AN:

152274

Hom.:

Cov.:

AF XY:

0.00911

AC XY:

678

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00356

Gnomad4 AMR

AF:

0.0127

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00518

Gnomad4 NFE

AF:

0.0146

Gnomad4 OTH

AF:

0.00994

Alfa

AF:

0.0126

Hom.:

Bravo

AF:

0.0104

Asia WGS

AF:

0.000866

AC:

AN:

3478

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 submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

DNAH10: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.4

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000092

dbscSNV1_RF

Benign

0.0020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over