NM_001372106.1:c.682T>C

Variant names:

• chr12-123781140-T-C
• rs11057353
• NM_001372106.1:c.682T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001372106.1(DNAH10):​c.682T>C​(p.Ser228Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 1,613,600 control chromosomes in the GnomAD database, including 325,110 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (30974 hom., cov: 30)
  • Exomes 𝑓: 0.63 (294136 hom.)
• Consequence: DNAH10 NM_001372106.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.47
• Publications: 39 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1367255E-6).
• BP6: Variant 12-123781140-T-C is Benign according to our data. Variant chr12-123781140-T-C is described in ClinVar as Benign. ClinVar VariationId is 402611.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.922 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH10	NM_001372106.1	MANE Select	c.682T>C	p.Ser228Pro	missense	Exon 6 of 79	NP_001359035.1
	DNAH10	NM_207437.3		c.499T>C	p.Ser167Pro	missense	Exon 6 of 78	NP_997320.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH10	ENST00000673944.1	MANE Select	c.682T>C	p.Ser228Pro	missense	Exon 6 of 79	ENSP00000501095.1
	DNAH10	ENST00000447853.2	TSL:1	n.14T>C		non_coding_transcript_exon	Exon 1 of 15
	DNAH10	ENST00000409039.8	TSL:5	c.682T>C	p.Ser228Pro	missense	Exon 6 of 78	ENSP00000386770.4

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96171 AN: 151764 Hom.: 30940 Cov.: 30

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.945

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.644

GnomAD2 exomes AF: 0.667 AC: 167460 AN: 251206 AF XY: 0.666

Gnomad AFR exome AF: 0.556

Gnomad AMR exome AF: 0.696

Gnomad ASJ exome AF: 0.684

Gnomad EAS exome AF: 0.949

Gnomad FIN exome AF: 0.659

Gnomad NFE exome AF: 0.626

Gnomad OTH exome AF: 0.652

GnomAD4 exome AF: 0.631 AC: 922399 AN: 1461720 Hom.: 294136 Cov.: 62 AF XY: 0.633 AC XY: 460440 AN XY: 727162

African (AFR) AF: 0.551 AC: 18438 AN: 33476

American (AMR) AF: 0.698 AC: 31208 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 17916 AN: 26130

East Asian (EAS) AF: 0.950 AC: 37710 AN: 39698

South Asian (SAS) AF: 0.671 AC: 57872 AN: 86250

European-Finnish (FIN) AF: 0.667 AC: 35617 AN: 53408

Middle Eastern (MID) AF: 0.592 AC: 3414 AN: 5768

European-Non Finnish (NFE) AF: 0.613 AC: 681331 AN: 1111886

Other (OTH) AF: 0.644 AC: 38893 AN: 60386

GnomAD4 genome AF: 0.634 AC: 96251 AN: 151880 Hom.: 30974 Cov.: 30 AF XY: 0.640 AC XY: 47528 AN XY: 74222

African (AFR) AF: 0.565 AC: 23374 AN: 41362

American (AMR) AF: 0.693 AC: 10572 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2380 AN: 3472

East Asian (EAS) AF: 0.945 AC: 4885 AN: 5172

South Asian (SAS) AF: 0.703 AC: 3375 AN: 4804

European-Finnish (FIN) AF: 0.670 AC: 7062 AN: 10544

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42515 AN: 67952

Other (OTH) AF: 0.648 AC: 1363 AN: 2104

Alfa AF: 0.636 Hom.: 94442

Bravo AF: 0.631

TwinsUK AF: 0.612 AC: 2268

ALSPAC AF: 0.604 AC: 2326

ESP6500AA AF: 0.560 AC: 2468

ESP6500EA AF: 0.630 AC: 5418

ExAC AF: 0.663 AC: 80462

Asia WGS AF: 0.808 AC: 2808 AN: 3478

EpiCase AF: 0.622

EpiControl AF: 0.630

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Apr 19, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30389748, 31178129)

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.062
DANN	Benign	0.68
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.32	N
PhyloP100		-1.5
PrimateAI	Benign	0.34	T
REVEL	Benign	0.071
Polyphen		0.0	B
MPC		0.18
ClinPred		0.026	T
GERP RS		-11
Varity_R		0.064
gMVP		0.23
Mutation Taster		=91/9	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11057353; hg19: chr12-124265687; COSMIC: COSV68997523;