3-52322110-G-A

Position:

• chr3-52322110-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_015512.5(DNAH1):​c.-34-299G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 152,256 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.012 (17 hom., cov: 32)
• Consequence: DNAH1 NM_015512.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.32

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-52322110-G-A is Benign according to our data. Variant chr3-52322110-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1218326.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0118 (1795/152256) while in subpopulation SAS AF= 0.0334 (161/4818). AF 95% confidence interval is 0.0292. There are 17 homozygotes in gnomad4. There are 853 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH1	NM_015512.5	c.-34-299G>A		intron_variant		ENST00000420323.7	NP_056327.4
DNAH1	XM_017006129.2	c.-34-299G>A		intron_variant			XP_016861618.1
DNAH1	XM_017006130.2	c.-34-299G>A		intron_variant			XP_016861619.1
DNAH1	XM_017006131.2	c.-34-299G>A		intron_variant			XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH1	ENST00000420323.7	c.-34-299G>A		intron_variant		1	NM_015512.5	ENSP00000401514	P1
DNAH1	ENST00000486752.5	n.228-299G>A		intron_variant, non_coding_transcript_variant		2
DNAH1	ENST00000497875.1	n.132-299G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1797 AN: 152138 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.00280

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0332

Gnomad FIN AF: 0.00406

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0172

Gnomad OTH AF: 0.0163

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

GnomAD4 genome AF: 0.0118 AC: 1795 AN: 152256 Hom.: 17 Cov.: 32 AF XY: 0.0115 AC XY: 853 AN XY: 74438

Gnomad4 AFR AF: 0.00279

Gnomad4 AMR AF: 0.0120

Gnomad4 ASJ AF: 0.0242

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0334

Gnomad4 FIN AF: 0.00406

Gnomad4 NFE AF: 0.0172

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0132 Hom.: 2

Bravo AF: 0.0112

Asia WGS AF: 0.0130 AC: 44 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.27
DANN	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs74762885; hg19: chr3-52356126;