rs6488908

Variant names:

• chr12-123893267-A-G
• rs6488908
• NM_001372106.1:c.9030A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001372106.1(DNAH10):​c.9030A>G​(p.Lys3010Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0605 in 1,613,944 control chromosomes in the GnomAD database, including 3,372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.077 (529 hom., cov: 33)
  • Exomes 𝑓: 0.059 (2843 hom.)
• Consequence: DNAH10 NM_001372106.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.04
• Publications: 6 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 12-123893267-A-G is Benign according to our data. Variant chr12-123893267-A-G is described in ClinVar as Benign. ClinVar VariationId is 402618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.04 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH10	NM_001372106.1	c.9030A>G	p.Lys3010Lys	synonymous_variant	Exon 53 of 79	ENST00000673944.1	NP_001359035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH10	ENST00000673944.1	c.9030A>G	p.Lys3010Lys	synonymous_variant	Exon 53 of 79		NM_001372106.1	ENSP00000501095.1
DNAH10	ENST00000409039.8	c.8859A>G	p.Lys2953Lys	synonymous_variant	Exon 52 of 78	5		ENSP00000386770.4
DNAH10	ENST00000638045.1	c.8676A>G	p.Lys2892Lys	synonymous_variant	Exon 52 of 78	5		ENSP00000489675.1

Frequencies

GnomAD3 genomes AF: 0.0765 AC: 11643 AN: 152188 Hom.: 528 Cov.: 33

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0512

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0271

Gnomad FIN AF: 0.0691

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0623

Gnomad OTH AF: 0.0774

GnomAD2 exomes AF: 0.0548 AC: 13645 AN: 249066 AF XY: 0.0543

Gnomad AFR exome AF: 0.133

Gnomad AMR exome AF: 0.0331

Gnomad ASJ exome AF: 0.0344

Gnomad EAS exome AF: 0.000946

Gnomad FIN exome AF: 0.0671

Gnomad NFE exome AF: 0.0656

Gnomad OTH exome AF: 0.0597

GnomAD4 exome AF: 0.0588 AC: 86013 AN: 1461638 Hom.: 2843 Cov.: 33 AF XY: 0.0580 AC XY: 42170 AN XY: 727102

African (AFR) AF: 0.132 AC: 4434 AN: 33476

American (AMR) AF: 0.0349 AC: 1561 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0364 AC: 952 AN: 26136

East Asian (EAS) AF: 0.000730 AC: 29 AN: 39700

South Asian (SAS) AF: 0.0299 AC: 2582 AN: 86258

European-Finnish (FIN) AF: 0.0712 AC: 3801 AN: 53402

Middle Eastern (MID) AF: 0.0469 AC: 270 AN: 5760

European-Non Finnish (NFE) AF: 0.0619 AC: 68845 AN: 1111812

Other (OTH) AF: 0.0586 AC: 3539 AN: 60374

GnomAD4 genome AF: 0.0766 AC: 11663 AN: 152306 Hom.: 529 Cov.: 33 AF XY: 0.0736 AC XY: 5486 AN XY: 74492

African (AFR) AF: 0.129 AC: 5361 AN: 41544

American (AMR) AF: 0.0511 AC: 783 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5184

South Asian (SAS) AF: 0.0269 AC: 130 AN: 4828

European-Finnish (FIN) AF: 0.0691 AC: 734 AN: 10620

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0623 AC: 4237 AN: 68028

Other (OTH) AF: 0.0766 AC: 162 AN: 2114

Alfa AF: 0.0697 Hom.: 413

Bravo AF: 0.0781

Asia WGS AF: 0.0270 AC: 95 AN: 3478

EpiCase AF: 0.0602

EpiControl AF: 0.0584

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.0
DANN	Benign	0.53
PhyloP100		2.0
Mutation Taster		=98/2	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: rs6488908; hg19: chr12-124377814;