12-123783156-T-C

Variant names:

• chr12-123783156-T-C
• rs11057355
• NM_001372106.1:c.891T>C

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.891T>C​(p.Ser297Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 1,613,770 control chromosomes in the GnomAD database, including 318,239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (36227 hom., cov: 32)
  • Exomes 𝑓: 0.62 (282012 hom.)
• Consequence: DNAH10 NM_001372106.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.47
• Publications: 19 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

LOC105370044 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 12-123783156-T-C is Benign according to our data. Variant chr12-123783156-T-C is described in ClinVar as Benign. ClinVar VariationId is 402613.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.47 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH10	NM_001372106.1	c.891T>C	p.Ser297Ser	synonymous_variant	Exon 7 of 79	ENST00000673944.1	NP_001359035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH10	ENST00000673944.1	c.891T>C	p.Ser297Ser	synonymous_variant	Exon 7 of 79		NM_001372106.1	ENSP00000501095.1

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103481 AN: 151948 Hom.: 36168 Cov.: 32

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.680

GnomAD2 exomes AF: 0.673 AC: 169105 AN: 251448 AF XY: 0.666

Gnomad AFR exome AF: 0.786

Gnomad AMR exome AF: 0.729

Gnomad ASJ exome AF: 0.694

Gnomad EAS exome AF: 0.999

Gnomad FIN exome AF: 0.604

Gnomad NFE exome AF: 0.593

Gnomad OTH exome AF: 0.646

GnomAD4 exome AF: 0.615 AC: 899276 AN: 1461704 Hom.: 282012 Cov.: 49 AF XY: 0.617 AC XY: 448832 AN XY: 727182

African (AFR) AF: 0.792 AC: 26499 AN: 33472

American (AMR) AF: 0.729 AC: 32609 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 18187 AN: 26134

East Asian (EAS) AF: 0.999 AC: 39662 AN: 39700

South Asian (SAS) AF: 0.692 AC: 59666 AN: 86252

European-Finnish (FIN) AF: 0.609 AC: 32504 AN: 53412

Middle Eastern (MID) AF: 0.619 AC: 3568 AN: 5768

European-Non Finnish (NFE) AF: 0.583 AC: 647782 AN: 1111854

Other (OTH) AF: 0.642 AC: 38799 AN: 60390

GnomAD4 genome AF: 0.681 AC: 103595 AN: 152066 Hom.: 36227 Cov.: 32 AF XY: 0.686 AC XY: 50967 AN XY: 74340

African (AFR) AF: 0.786 AC: 32578 AN: 41468

American (AMR) AF: 0.722 AC: 11026 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2399 AN: 3468

East Asian (EAS) AF: 0.996 AC: 5151 AN: 5174

South Asian (SAS) AF: 0.721 AC: 3478 AN: 4826

European-Finnish (FIN) AF: 0.610 AC: 6458 AN: 10580

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40445 AN: 67958

Other (OTH) AF: 0.684 AC: 1444 AN: 2110

Alfa AF: 0.633 Hom.: 83729

Bravo AF: 0.693

Asia WGS AF: 0.867 AC: 3012 AN: 3478

EpiCase AF: 0.595

EpiControl AF: 0.607

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	-0.93
CADD	Benign	0.0050
DANN	Benign	0.46
PhyloP100		-3.5
Mutation Taster		=46/54	disease causing

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: rs11057355; hg19: chr12-124267703; COSMIC: COSV108245364;