chr3-52343278-A-G

Position:

• chr3-52343278-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH1	NM_015512.5	c.1287-1212A>G		intron_variant		ENST00000420323.7	NP_056327.4
DNAH1	XM_017006129.2	c.1287-1212A>G		intron_variant			XP_016861618.1
DNAH1	XM_017006130.2	c.1287-1212A>G		intron_variant			XP_016861619.1
DNAH1	XM_017006131.2	c.1287-1212A>G		intron_variant			XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH1	ENST00000420323.7	c.1287-1212A>G		intron_variant		1	NM_015512.5	ENSP00000401514	P1
DNAH1	ENST00000486752.5	n.1548-1212A>G		intron_variant, non_coding_transcript_variant		2
DNAH1	ENST00000497875.1	n.1452-1212A>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.572

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.0330

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.0846

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.259

Alfa AF: 0.198 Hom.: 1834

Bravo AF: 0.295

Asia WGS AF: 0.120 AC: 416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs13091545; hg19: chr3-52377294;