rs11057354

Variant names:

• chr12-123783091-A-G
• rs11057354
• NM_001372106.1:c.842-16A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-123783091-A-G
• chr12-123783091-A-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.842-16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 1,611,744 control chromosomes in the GnomAD database, including 652,724 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.92 (64640 hom., cov: 32)
  • Exomes 𝑓: 0.90 (588084 hom.)
• Consequence: DNAH10 NM_001372106.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.77
• Publications: 16 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 (BayesDel_noAF=-0.9).
• BP6: Variant 12-123783091-A-G is Benign according to our data. Variant chr12-123783091-A-G is described in ClinVar as Benign. ClinVar VariationId is 402612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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.842-16A>G		intron	N/A	NP_001359035.1
	DNAH10	NM_207437.3		c.659-16A>G		intron	N/A	NP_997320.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH10	ENST00000673944.1	MANE Select	c.842-16A>G		intron	N/A	ENSP00000501095.1
	DNAH10	ENST00000447853.2	TSL:1	n.174-16A>G		intron	N/A
	DNAH10	ENST00000409039.8	TSL:5	c.842-16A>G		intron	N/A	ENSP00000386770.4

Frequencies

GnomAD3 genomes AF: 0.920 AC: 139914 AN: 152102 Hom.: 64585 Cov.: 32

Gnomad AFR AF: 0.980

Gnomad AMI AF: 0.925

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.947

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.966

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.892

Gnomad OTH AF: 0.939

GnomAD2 exomes AF: 0.907 AC: 227423 AN: 250710 AF XY: 0.910

Gnomad AFR exome AF: 0.982

Gnomad AMR exome AF: 0.863

Gnomad ASJ exome AF: 0.943

Gnomad EAS exome AF: 0.999

Gnomad FIN exome AF: 0.811

Gnomad NFE exome AF: 0.896

Gnomad OTH exome AF: 0.911

GnomAD4 exome AF: 0.897 AC: 1309042 AN: 1459524 Hom.: 588084 Cov.: 34 AF XY: 0.899 AC XY: 653072 AN XY: 726072

African (AFR) AF: 0.983 AC: 32905 AN: 33458

American (AMR) AF: 0.870 AC: 38838 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.940 AC: 24548 AN: 26112

East Asian (EAS) AF: 1.00 AC: 39673 AN: 39686

South Asian (SAS) AF: 0.957 AC: 82418 AN: 86126

European-Finnish (FIN) AF: 0.819 AC: 43728 AN: 53404

Middle Eastern (MID) AF: 0.968 AC: 5581 AN: 5766

European-Non Finnish (NFE) AF: 0.889 AC: 986337 AN: 1110020

Other (OTH) AF: 0.912 AC: 55014 AN: 60318

GnomAD4 genome AF: 0.920 AC: 140027 AN: 152220 Hom.: 64640 Cov.: 32 AF XY: 0.918 AC XY: 68315 AN XY: 74418

African (AFR) AF: 0.980 AC: 40732 AN: 41550

American (AMR) AF: 0.906 AC: 13838 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.947 AC: 3287 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5177 AN: 5186

South Asian (SAS) AF: 0.964 AC: 4648 AN: 4820

European-Finnish (FIN) AF: 0.811 AC: 8576 AN: 10578

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.892 AC: 60653 AN: 68024

Other (OTH) AF: 0.940 AC: 1982 AN: 2108

Alfa AF: 0.903 Hom.: 46400

Bravo AF: 0.928

Asia WGS AF: 0.980 AC: 3408 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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0060
DANN	Benign	0.28
PhyloP100		-1.8
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: rs11057354; hg19: chr12-124267638;