chr12-123903122-C-T

Variant names:

• chr12-123903122-C-T
• rs75558206
• NM_001372106.1:c.9815+9C>T

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.9815+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0418 in 1,600,364 control chromosomes in the GnomAD database, including 4,711 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (2119 hom., cov: 33)
  • Exomes 𝑓: 0.035 (2592 hom.)
• Consequence: DNAH10 NM_001372106.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0920
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 12-123903122-C-T is Benign according to our data. Variant chr12-123903122-C-T is described in ClinVar as [Benign]. Clinvar id is 402623.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH10	NM_001372106.1	c.9815+9C>T		intron_variant	Intron 57 of 78	ENST00000673944.1	NP_001359035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH10	ENST00000673944.1	c.9815+9C>T		intron_variant	Intron 57 of 78		NM_001372106.1	ENSP00000501095.1
DNAH10	ENST00000409039.8	c.9644+9C>T		intron_variant	Intron 56 of 77	5		ENSP00000386770.4
DNAH10	ENST00000638045.1	c.9461+9C>T		intron_variant	Intron 56 of 77	5		ENSP00000489675.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16476 AN: 152080 Hom.: 2113 Cov.: 33

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0678

Gnomad ASJ AF: 0.0769

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.0174

Gnomad FIN AF: 0.00434

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0277

Gnomad OTH AF: 0.101

GnomAD2 exomes AF: 0.0423 AC: 9608 AN: 227000 AF XY: 0.0379

Gnomad AFR exome AF: 0.314

Gnomad AMR exome AF: 0.0409

Gnomad ASJ exome AF: 0.0685

Gnomad EAS exome AF: 0.000833

Gnomad FIN exome AF: 0.00418

Gnomad NFE exome AF: 0.0256

Gnomad OTH exome AF: 0.0436

GnomAD4 exome AF: 0.0348 AC: 50390 AN: 1448166 Hom.: 2592 Cov.: 32 AF XY: 0.0336 AC XY: 24155 AN XY: 718816

African (AFR) AF: 0.331 AC: 10952 AN: 33096

American (AMR) AF: 0.0426 AC: 1841 AN: 43174

Ashkenazi Jewish (ASJ) AF: 0.0710 AC: 1829 AN: 25772

East Asian (EAS) AF: 0.000613 AC: 24 AN: 39176

South Asian (SAS) AF: 0.0198 AC: 1660 AN: 83892

European-Finnish (FIN) AF: 0.00422 AC: 219 AN: 51956

Middle Eastern (MID) AF: 0.0727 AC: 418 AN: 5746

European-Non Finnish (NFE) AF: 0.0275 AC: 30418 AN: 1105448

Other (OTH) AF: 0.0506 AC: 3029 AN: 59906

GnomAD4 genome AF: 0.108 AC: 16506 AN: 152198 Hom.: 2119 Cov.: 33 AF XY: 0.105 AC XY: 7776 AN XY: 74410

African (AFR) AF: 0.311 AC: 12900 AN: 41476

American (AMR) AF: 0.0677 AC: 1036 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0769 AC: 267 AN: 3470

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5176

South Asian (SAS) AF: 0.0172 AC: 83 AN: 4826

European-Finnish (FIN) AF: 0.00434 AC: 46 AN: 10610

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0277 AC: 1883 AN: 68018

Other (OTH) AF: 0.101 AC: 213 AN: 2114

Alfa AF: 0.0468 Hom.: 848

Bravo AF: 0.124

Asia WGS AF: 0.0340 AC: 118 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	-0.81
CADD	Benign	3.9
DANN	Benign	0.22
PhyloP100		-0.092
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: rs75558206; hg19: chr12-124387669;