rs13091545

Variant names:

• chr3-52343278-A-G
• rs13091545
• NM_015512.5:c.1287-1212A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015512.5(DNAH1):​c.1287-1212A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,052 control chromosomes in the GnomAD database, including 8,389 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (8389 hom., cov: 32)
• Consequence: DNAH1 NM_015512.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87
• Publications: 9 publications found

Genes affected

DNAH1 (HGNC:2940): (dynein axonemal heavy chain 1) This gene encodes an inner dynein arm heavy chain that provides structural support between the radial spokes and the outer doublet of the sperm tail. Naturally occurring mutations in this gene are associated with primary ciliary dyskinesia and multiple morphological anomalies of the flagella that result in asthenozoospermia and male infertility. Mice with a homozygous knockout of the orthologous gene are viable but have reduced sperm motility and are infertile. [provided by RefSeq, Feb 2017]

DNAH1 Gene-Disease associations (from GenCC):

• spermatogenic failure 18

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• ciliary dyskinesia, primary, 37

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015512.5. 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
	DNAH1	NM_015512.5	MANE Select	c.1287-1212A>G		intron	N/A	NP_056327.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH1	ENST00000420323.7	TSL:1 MANE Select	c.1287-1212A>G		intron	N/A	ENSP00000401514.2
	DNAH1	ENST00000486752.5	TSL:2	n.1548-1212A>G		intron	N/A
	DNAH1	ENST00000497875.1	TSL:2	n.1452-1212A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41519 AN: 151934 Hom.: 8355 Cov.: 32

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0333

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0846

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.259

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.274 AC: 41603 AN: 152052 Hom.: 8389 Cov.: 32 AF XY: 0.264 AC XY: 19614 AN XY: 74364

African (AFR) AF: 0.572 AC: 23663 AN: 41392

American (AMR) AF: 0.181 AC: 2773 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 559 AN: 3470

East Asian (EAS) AF: 0.0330 AC: 171 AN: 5182

South Asian (SAS) AF: 0.128 AC: 616 AN: 4826

European-Finnish (FIN) AF: 0.0846 AC: 897 AN: 10602

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12175 AN: 67972

Other (OTH) AF: 0.259 AC: 547 AN: 2114

Alfa AF: 0.197 Hom.: 1978

Bravo AF: 0.295

Asia WGS AF: 0.120 AC: 416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.71
PhyloP100		-1.9
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: rs13091545; hg19: chr3-52377294;