rs7978454

Variant names:

• chr12-123832329-A-G
• rs7978454
• NM_001372106.1:c.4546-785A>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.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
• Publications: 10 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: MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics
• primary ciliary dyskinesia

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH10	NM_001372106.1	MANE Select	c.4546-785A>G		intron	N/A	NP_001359035.1	A0A669KB38
	DNAH10	NM_207437.3		c.4192-785A>G		intron	N/A	NP_997320.2	B0I1S1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH10	ENST00000673944.1	MANE Select	c.4546-785A>G		intron	N/A	ENSP00000501095.1	A0A669KB38
	DNAH10	ENST00000409039.8	TSL:5	c.4375-785A>G		intron	N/A	ENSP00000386770.4	A0A1C7CYW8
	DNAH10	ENST00000638045.1	TSL:5	c.4192-785A>G		intron	N/A	ENSP00000489675.1	Q8IVF4-1

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

African (AFR) AF: 0.666 AC: 27574 AN: 41428

American (AMR) AF: 0.378 AC: 5784 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1412 AN: 3468

East Asian (EAS) AF: 0.0569 AC: 295 AN: 5184

South Asian (SAS) AF: 0.323 AC: 1556 AN: 4822

European-Finnish (FIN) AF: 0.395 AC: 4173 AN: 10554

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30208 AN: 67968

Other (OTH) AF: 0.449 AC: 949 AN: 2112

Alfa AF: 0.459 Hom.: 38453

Bravo AF: 0.488

Asia WGS AF: 0.221 AC: 771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.33
PhyloP100		-0.34
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: rs7978454; hg19: chr12-124316876;