3-52366724-G-C

Position:

• chr3-52366724-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015512.5(DNAH1):​c.5611-9G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,603,666 control chromosomes in the GnomAD database, including 23,378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2723 hom., cov: 32)
  • Exomes 𝑓: 0.16 (20655 hom.)
• Consequence: DNAH1 NM_015512.5 intron
• Scores: Splicing: ADA: 0.00001498
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.375

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 3-52366724-G-C is Benign according to our data. Variant chr3-52366724-G-C is described in ClinVar as [Benign]. Clinvar id is 402599.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH1	NM_015512.5	c.5611-9G>C		intron_variant		ENST00000420323.7	NP_056327.4
DNAH1	XM_017006129.2	c.5611-9G>C		intron_variant			XP_016861618.1
DNAH1	XM_017006130.2	c.5611-9G>C		intron_variant			XP_016861619.1
DNAH1	XM_017006131.2	c.5611-9G>C		intron_variant			XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH1	ENST00000420323.7	c.5611-9G>C		intron_variant		1	NM_015512.5	ENSP00000401514.2
DNAH1	ENST00000486752.5	n.5872-9G>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.178 AC: 26933 AN: 151496 Hom.: 2719 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.0229

Gnomad SAS AF: 0.0888

Gnomad FIN AF: 0.0834

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.190

GnomAD3 exomes AF: 0.136 AC: 33304 AN: 244968 Hom.: 2674 AF XY: 0.134 AC XY: 17802 AN XY: 132758

Gnomad AFR exome AF: 0.260

Gnomad AMR exome AF: 0.109

Gnomad ASJ exome AF: 0.151

Gnomad EAS exome AF: 0.0182

Gnomad SAS exome AF: 0.0921

Gnomad FIN exome AF: 0.0887

Gnomad NFE exome AF: 0.165

Gnomad OTH exome AF: 0.146

GnomAD4 exome AF: 0.163 AC: 236378 AN: 1452052 Hom.: 20655 Cov.: 36 AF XY: 0.160 AC XY: 115526 AN XY: 720770

Gnomad4 AFR exome AF: 0.270

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.151

Gnomad4 EAS exome AF: 0.0170

Gnomad4 SAS exome AF: 0.0957

Gnomad4 FIN exome AF: 0.0926

Gnomad4 NFE exome AF: 0.175

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.178 AC: 26954 AN: 151614 Hom.: 2723 Cov.: 32 AF XY: 0.171 AC XY: 12659 AN XY: 74102

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.0226

Gnomad4 SAS AF: 0.0893

Gnomad4 FIN AF: 0.0834

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.190

Alfa AF: 0.101 Hom.: 189

Bravo AF: 0.186

Asia WGS AF: 0.0810 AC: 283 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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 -

Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0040
DANN	Benign	0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000015
dbscSNV1_RF	Benign	0.0
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: rs3752819; hg19: chr3-52400740; COSMIC: COSV70239289; COSMIC: COSV70239289;