rs61587964

chr12-123903039-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001372106.1(DNAH10):c.9741A>G(p.Ala3247=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,606,932 control chromosomes in the GnomAD database, including 53,179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (9454 hom., cov: 32)
  • Exomes 𝑓: 0.24 (43725 hom.)
• Consequence: DNAH10 NM_001372106.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.25

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 12-123903039-A-G is Benign according to our data. Variant chr12-123903039-A-G is described in ClinVar as [Benign]. Clinvar id is 402622.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-123903039-A-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-2.25 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH10	NM_001372106.1	c.9741A>G	p.Ala3247=	synonymous_variant	57/79	ENST00000673944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH10	ENST00000673944.1	c.9741A>G	p.Ala3247=	synonymous_variant	57/79		NM_001372106.1	P1
DNAH10	ENST00000409039.8	c.9570A>G	p.Ala3190=	synonymous_variant	56/78	5
DNAH10	ENST00000638045.1	c.9387A>G	p.Ala3129=	synonymous_variant	56/78	5

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49067 AN: 151826 Hom.: 9435 Cov.: 32

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.317

GnomAD3 exomes AF: 0.252 AC: 60052 AN: 238504 Hom.: 8132 AF XY: 0.246 AC XY: 31823 AN XY: 129182

Gnomad AFR exome AF: 0.553

Gnomad AMR exome AF: 0.256

Gnomad ASJ exome AF: 0.219

Gnomad EAS exome AF: 0.252

Gnomad SAS exome AF: 0.235

Gnomad FIN exome AF: 0.232

Gnomad NFE exome AF: 0.222

Gnomad OTH exome AF: 0.249

GnomAD4 exome AF: 0.240 AC: 348745 AN: 1454988 Hom.: 43725 Cov.: 34 AF XY: 0.239 AC XY: 172502 AN XY: 722996

Gnomad4 AFR exome AF: 0.565

Gnomad4 AMR exome AF: 0.258

Gnomad4 ASJ exome AF: 0.219

Gnomad4 EAS exome AF: 0.267

Gnomad4 SAS exome AF: 0.241

Gnomad4 FIN exome AF: 0.242

Gnomad4 NFE exome AF: 0.227

Gnomad4 OTH exome AF: 0.261

GnomAD4 genome AF: 0.323 AC: 49140 AN: 151944 Hom.: 9454 Cov.: 32 AF XY: 0.321 AC XY: 23825 AN XY: 74286

Gnomad4 AFR AF: 0.549

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.315

Alfa AF: 0.266 Hom.: 3190

Bravo AF: 0.337

Asia WGS AF: 0.311 AC: 1079 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.086
Dann	Benign	0.35

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: rs61587964; hg19: chr12-124387586; COSMIC: COSV68989775;