12-123890663-A-G

Variant names:

• chr12-123890663-A-G
• rs10773046
• NM_001372106.1:c.8996-2570A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001372106.1(DNAH10):​c.8996-2570A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 151,962 control chromosomes in the GnomAD database, including 16,235 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 0.46 (16235 hom., cov: 31)
• Consequence: DNAH10 NM_001372106.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• spermatogenic failure 56

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372106.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH10	NM_001372106.1	MANE Select	c.8996-2570A>G		intron	N/A	NP_001359035.1
	DNAH10	NM_207437.3		c.8642-2570A>G		intron	N/A	NP_997320.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH10	ENST00000673944.1	MANE Select	c.8996-2570A>G		intron	N/A	ENSP00000501095.1
	DNAH10	ENST00000409039.8	TSL:5	c.8825-2570A>G		intron	N/A	ENSP00000386770.4
	DNAH10	ENST00000638045.1	TSL:5	c.8642-2570A>G		intron	N/A	ENSP00000489675.1

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69798 AN: 151844 Hom.: 16207 Cov.: 31

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.460 AC: 69880 AN: 151962 Hom.: 16235 Cov.: 31 AF XY: 0.454 AC XY: 33737 AN XY: 74256

African (AFR) AF: 0.505 AC: 20920 AN: 41442

American (AMR) AF: 0.441 AC: 6726 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1333 AN: 3466

East Asian (EAS) AF: 0.281 AC: 1453 AN: 5164

South Asian (SAS) AF: 0.377 AC: 1810 AN: 4804

European-Finnish (FIN) AF: 0.448 AC: 4724 AN: 10552

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31364 AN: 67952

Other (OTH) AF: 0.453 AC: 957 AN: 2114

Alfa AF: 0.462 Hom.: 28815

Bravo AF: 0.465

Asia WGS AF: 0.371 AC: 1287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.24
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10773046; hg19: chr12-124375210;