rs1316952

Variant names:

• chr12-123915003-T-C
• rs1316952
• NM_001372106.1:c.10722+4T>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.10722+4T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,601,102 control chromosomes in the GnomAD database, including 22,462 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (5513 hom., cov: 32)
  • Exomes 𝑓: 0.14 (16949 hom.)
• Consequence: DNAH10 NM_001372106.1 splice_region, intron
• Scores: Splicing: ADA: 0.00001263
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.43
• Publications: 28 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=-0.92).
• BP6: Variant 12-123915003-T-C is Benign according to our data. Variant chr12-123915003-T-C is described in ClinVar as [Benign]. Clinvar id is 402624.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH10	NM_001372106.1	c.10722+4T>C		splice_region_variant, intron_variant	Intron 62 of 78	ENST00000673944.1	NP_001359035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH10	ENST00000673944.1	c.10722+4T>C		splice_region_variant, intron_variant	Intron 62 of 78		NM_001372106.1	ENSP00000501095.1
DNAH10	ENST00000409039.8	c.10551+4T>C		splice_region_variant, intron_variant	Intron 61 of 77	5		ENSP00000386770.4
DNAH10	ENST00000638045.1	c.10368+4T>C		splice_region_variant, intron_variant	Intron 61 of 77	5		ENSP00000489675.1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33710 AN: 152000 Hom.: 5500 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0771

Gnomad FIN AF: 0.0884

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.220

GnomAD2 exomes AF: 0.133 AC: 30134 AN: 225836 AF XY: 0.129

Gnomad AFR exome AF: 0.472

Gnomad AMR exome AF: 0.0986

Gnomad ASJ exome AF: 0.233

Gnomad EAS exome AF: 0.00109

Gnomad FIN exome AF: 0.0917

Gnomad NFE exome AF: 0.136

Gnomad OTH exome AF: 0.142

GnomAD4 exome AF: 0.139 AC: 201002 AN: 1448984 Hom.: 16949 Cov.: 32 AF XY: 0.137 AC XY: 98291 AN XY: 719716

African (AFR) AF: 0.471 AC: 15568 AN: 33028

American (AMR) AF: 0.106 AC: 4535 AN: 42966

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 6218 AN: 25722

East Asian (EAS) AF: 0.000894 AC: 35 AN: 39156

South Asian (SAS) AF: 0.0810 AC: 6814 AN: 84124

European-Finnish (FIN) AF: 0.0956 AC: 5002 AN: 52340

Middle Eastern (MID) AF: 0.192 AC: 1100 AN: 5740

European-Non Finnish (NFE) AF: 0.138 AC: 152495 AN: 1106008

Other (OTH) AF: 0.154 AC: 9235 AN: 59900

GnomAD4 genome AF: 0.222 AC: 33767 AN: 152118 Hom.: 5513 Cov.: 32 AF XY: 0.213 AC XY: 15878 AN XY: 74370

African (AFR) AF: 0.460 AC: 19047 AN: 41448

American (AMR) AF: 0.150 AC: 2298 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 853 AN: 3472

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5178

South Asian (SAS) AF: 0.0771 AC: 372 AN: 4822

European-Finnish (FIN) AF: 0.0884 AC: 937 AN: 10602

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9502 AN: 68000

Other (OTH) AF: 0.219 AC: 462 AN: 2114

Alfa AF: 0.174 Hom.: 9176

Bravo AF: 0.241

Asia WGS AF: 0.0770 AC: 269 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	-0.92
CADD	Benign	0.0020
DANN	Benign	0.55
PhyloP100		-4.4
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000013
dbscSNV1_RF	Benign	0.0060
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: rs1316952; hg19: chr12-124399550;