12-123903027-G-A

Variant names:

• chr12-123903027-G-A
• rs58411567
• NM_001372106.1:c.9729G>A

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.9729G>A​(p.Glu3243Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,604,564 control chromosomes in the GnomAD database, including 49,530 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7823 hom., cov: 33)
  • Exomes 𝑓: 0.24 (41707 hom.)
• Consequence: DNAH10 NM_001372106.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.983
• Publications: 11 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=-0.52).
• BP6: Variant 12-123903027-G-A is Benign according to our data. Variant chr12-123903027-G-A is described in ClinVar as [Benign]. Clinvar id is 402621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.983 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH10	NM_001372106.1	c.9729G>A	p.Glu3243Glu	synonymous_variant	Exon 57 of 79	ENST00000673944.1	NP_001359035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH10	ENST00000673944.1	c.9729G>A	p.Glu3243Glu	synonymous_variant	Exon 57 of 79		NM_001372106.1	ENSP00000501095.1
DNAH10	ENST00000409039.8	c.9558G>A	p.Glu3186Glu	synonymous_variant	Exon 56 of 78	5		ENSP00000386770.4
DNAH10	ENST00000638045.1	c.9375G>A	p.Glu3125Glu	synonymous_variant	Exon 56 of 78	5		ENSP00000489675.1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45869 AN: 151810 Hom.: 7816 Cov.: 33

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.305

GnomAD2 exomes AF: 0.246 AC: 57839 AN: 234970 AF XY: 0.242

Gnomad AFR exome AF: 0.482

Gnomad AMR exome AF: 0.253

Gnomad ASJ exome AF: 0.209

Gnomad EAS exome AF: 0.252

Gnomad FIN exome AF: 0.225

Gnomad NFE exome AF: 0.222

Gnomad OTH exome AF: 0.247

GnomAD4 exome AF: 0.237 AC: 343905 AN: 1452636 Hom.: 41707 Cov.: 34 AF XY: 0.236 AC XY: 170277 AN XY: 721702

African (AFR) AF: 0.489 AC: 16245 AN: 33190

American (AMR) AF: 0.255 AC: 11050 AN: 43334

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 5408 AN: 25940

East Asian (EAS) AF: 0.266 AC: 10465 AN: 39280

South Asian (SAS) AF: 0.241 AC: 20404 AN: 84556

European-Finnish (FIN) AF: 0.235 AC: 12415 AN: 52754

Middle Eastern (MID) AF: 0.257 AC: 1479 AN: 5758

European-Non Finnish (NFE) AF: 0.227 AC: 251169 AN: 1107748

Other (OTH) AF: 0.254 AC: 15270 AN: 60076

GnomAD4 genome AF: 0.302 AC: 45916 AN: 151928 Hom.: 7823 Cov.: 33 AF XY: 0.300 AC XY: 22293 AN XY: 74284

African (AFR) AF: 0.478 AC: 19743 AN: 41334

American (AMR) AF: 0.262 AC: 4013 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 742 AN: 3470

East Asian (EAS) AF: 0.269 AC: 1386 AN: 5148

South Asian (SAS) AF: 0.249 AC: 1202 AN: 4820

European-Finnish (FIN) AF: 0.232 AC: 2453 AN: 10580

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15399 AN: 67978

Other (OTH) AF: 0.303 AC: 637 AN: 2104

Alfa AF: 0.257 Hom.: 2399

Bravo AF: 0.314

Asia WGS AF: 0.303 AC: 1051 AN: 3478

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	-0.52
CADD	Benign	1.8
DANN	Benign	0.39
PhyloP100		0.98
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: rs58411567; hg19: chr12-124387574; COSMIC: COSV68988100;