12-123832329-A-G

Position:

• chr12-123832329-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001372106.1(DNAH10):​c.4546-785A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 152,026 control chromosomes in the GnomAD database, including 18,915 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (18915 hom., cov: 32)
• Consequence: DNAH10 NM_001372106.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH10	NM_001372106.1	c.4546-785A>G		intron_variant		ENST00000673944.1	NP_001359035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH10	ENST00000673944.1	c.4546-785A>G		intron_variant			NM_001372106.1	ENSP00000501095	P1
DNAH10	ENST00000409039.8	c.4375-785A>G		intron_variant		5		ENSP00000386770
DNAH10	ENST00000638045.1	c.4192-785A>G		intron_variant		5		ENSP00000489675

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72481 AN: 151908 Hom.: 18881 Cov.: 32

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.0568

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.455

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.477 AC: 72556 AN: 152026 Hom.: 18915 Cov.: 32 AF XY: 0.467 AC XY: 34734 AN XY: 74344

Gnomad4 AFR AF: 0.666

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.0569

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.449

Alfa AF: 0.454 Hom.: 13992

Bravo AF: 0.488

Asia WGS AF: 0.221 AC: 771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.33

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

Other links and lift over

dbSNP: rs7978454; hg19: chr12-124316876;