rs114772660

Variant names:

• chr12-123893445-G-A
• rs114772660
• NM_001372106.1:c.9199+9G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-123893445-G-A
• chr12-123893445-G-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.9199+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0596 in 1,611,892 control chromosomes in the GnomAD database, including 3,238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.073 (466 hom., cov: 32)
  • Exomes 𝑓: 0.058 (2772 hom.)
• Consequence: DNAH10 NM_001372106.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.788
• 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=-0.85).
• BP6: Variant 12-123893445-G-A is Benign according to our data. Variant chr12-123893445-G-A is described in ClinVar as [Benign]. Clinvar id is 402619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH10	NM_001372106.1	c.9199+9G>A		intron_variant	Intron 53 of 78	ENST00000673944.1	NP_001359035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH10	ENST00000673944.1	c.9199+9G>A		intron_variant	Intron 53 of 78		NM_001372106.1	ENSP00000501095.1
DNAH10	ENST00000409039.8	c.9028+9G>A		intron_variant	Intron 52 of 77	5		ENSP00000386770.4
DNAH10	ENST00000638045.1	c.8845+9G>A		intron_variant	Intron 52 of 77	5		ENSP00000489675.1

Frequencies

GnomAD3 genomes AF: 0.0726 AC: 11045 AN: 152144 Hom.: 466 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0492

Gnomad ASJ AF: 0.0265

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0271

Gnomad FIN AF: 0.0695

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0620

Gnomad OTH AF: 0.0740

GnomAD2 exomes AF: 0.0533 AC: 13134 AN: 246320 AF XY: 0.0531

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.0317

Gnomad ASJ exome AF: 0.0259

Gnomad EAS exome AF: 0.000891

Gnomad FIN exome AF: 0.0671

Gnomad NFE exome AF: 0.0656

Gnomad OTH exome AF: 0.0590

GnomAD4 exome AF: 0.0583 AC: 85060 AN: 1459630 Hom.: 2772 Cov.: 32 AF XY: 0.0574 AC XY: 41700 AN XY: 726106

African (AFR) AF: 0.121 AC: 4053 AN: 33416

American (AMR) AF: 0.0335 AC: 1499 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0274 AC: 716 AN: 26134

East Asian (EAS) AF: 0.000705 AC: 28 AN: 39700

South Asian (SAS) AF: 0.0299 AC: 2579 AN: 86174

European-Finnish (FIN) AF: 0.0711 AC: 3788 AN: 53242

Middle Eastern (MID) AF: 0.0494 AC: 212 AN: 4294

European-Non Finnish (NFE) AF: 0.0618 AC: 68743 AN: 1111740

Other (OTH) AF: 0.0572 AC: 3442 AN: 60212

GnomAD4 genome AF: 0.0726 AC: 11058 AN: 152262 Hom.: 466 Cov.: 32 AF XY: 0.0703 AC XY: 5234 AN XY: 74458

African (AFR) AF: 0.117 AC: 4852 AN: 41532

American (AMR) AF: 0.0492 AC: 753 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0265 AC: 92 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5172

South Asian (SAS) AF: 0.0269 AC: 130 AN: 4832

European-Finnish (FIN) AF: 0.0695 AC: 738 AN: 10612

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0620 AC: 4218 AN: 68024

Other (OTH) AF: 0.0732 AC: 154 AN: 2104

Alfa AF: 0.0619 Hom.: 65

Bravo AF: 0.0738

Asia WGS AF: 0.0260 AC: 91 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	-0.85
CADD	Benign	2.2
DANN	Benign	0.36
PhyloP100		-0.79
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: rs114772660; hg19: chr12-124377992;