chr3-52394972-C-A

Variant names:

• chr3-52394972-C-A
• rs11708581
• NM_015512.5:c.10881C>A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_015512.5(DNAH1):​c.10881C>A​(p.Val3627Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,612,930 control chromosomes in the GnomAD database, including 10,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.077 (613 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10034 hom.)
• Consequence: DNAH1 NM_015512.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.81

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 3-52394972-C-A is Benign according to our data. Variant chr3-52394972-C-A is described in ClinVar as [Benign]. Clinvar id is 402603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.81 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH1	NM_015512.5	c.10881C>A	p.Val3627Val	synonymous_variant	Exon 68 of 78	ENST00000420323.7	NP_056327.4
DNAH1	XM_017006129.2	c.10950C>A	p.Val3650Val	synonymous_variant	Exon 70 of 80		XP_016861618.1
DNAH1	XM_017006130.2	c.10881C>A	p.Val3627Val	synonymous_variant	Exon 69 of 79		XP_016861619.1
DNAH1	XM_017006131.2	c.10824C>A	p.Val3608Val	synonymous_variant	Exon 69 of 79		XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH1	ENST00000420323.7	c.10881C>A	p.Val3627Val	synonymous_variant	Exon 68 of 78	1	NM_015512.5	ENSP00000401514.2

Frequencies

GnomAD3 genomes AF: 0.0770 AC: 11716 AN: 152194 Hom.: 614 Cov.: 32

Gnomad AFR AF: 0.0191

Gnomad AMI AF: 0.0716

Gnomad AMR AF: 0.0731

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0650

Gnomad FIN AF: 0.0522

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.101

GnomAD3 exomes AF: 0.0832 AC: 20532 AN: 246738 Hom.: 1036 AF XY: 0.0845 AC XY: 11320 AN XY: 134014

Gnomad AFR exome AF: 0.0171

Gnomad AMR exome AF: 0.0630

Gnomad ASJ exome AF: 0.119

Gnomad EAS exome AF: 0.000223

Gnomad SAS exome AF: 0.0710

Gnomad FIN exome AF: 0.0561

Gnomad NFE exome AF: 0.117

Gnomad OTH exome AF: 0.0924

GnomAD4 exome AF: 0.111 AC: 162647 AN: 1460618 Hom.: 10034 Cov.: 33 AF XY: 0.110 AC XY: 79981 AN XY: 726502

Gnomad4 AFR exome AF: 0.0183

Gnomad4 AMR exome AF: 0.0658

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.000302

Gnomad4 SAS exome AF: 0.0737

Gnomad4 FIN exome AF: 0.0588

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.0769 AC: 11712 AN: 152312 Hom.: 613 Cov.: 32 AF XY: 0.0741 AC XY: 5522 AN XY: 74476

Gnomad4 AFR AF: 0.0190

Gnomad4 AMR AF: 0.0730

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.000770

Gnomad4 SAS AF: 0.0657

Gnomad4 FIN AF: 0.0522

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.0998

Alfa AF: 0.103 Hom.: 1086

Bravo AF: 0.0756

Asia WGS AF: 0.0260 AC: 92 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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 -

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	1.7
DANN	Benign	0.74

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: rs11708581; hg19: chr3-52428988; COSMIC: COSV70229078; COSMIC: COSV70229078;