rs11708581

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-52394972-C-A
• chr3-52394972-C-G
• chr3-52394972-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 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 -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 VariationId 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

GnomAD2 exomes AF: 0.0832 AC: 20532 AN: 246738 AF XY: 0.0845

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 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

African (AFR) AF: 0.0183 AC: 612 AN: 33474

American (AMR) AF: 0.0658 AC: 2932 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 3109 AN: 26112

East Asian (EAS) AF: 0.000302 AC: 12 AN: 39686

South Asian (SAS) AF: 0.0737 AC: 6337 AN: 85998

European-Finnish (FIN) AF: 0.0588 AC: 3136 AN: 53288

Middle Eastern (MID) AF: 0.0987 AC: 569 AN: 5766

European-Non Finnish (NFE) AF: 0.126 AC: 139629 AN: 1111396

Other (OTH) AF: 0.105 AC: 6311 AN: 60330

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

African (AFR) AF: 0.0190 AC: 791 AN: 41582

American (AMR) AF: 0.0730 AC: 1117 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 436 AN: 3472

East Asian (EAS) AF: 0.000770 AC: 4 AN: 5192

South Asian (SAS) AF: 0.0657 AC: 317 AN: 4828

European-Finnish (FIN) AF: 0.0522 AC: 554 AN: 10622

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8184 AN: 68000

Other (OTH) AF: 0.0998 AC: 211 AN: 2114

Alfa AF: 0.100 Hom.: 1406

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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
PhyloP100		-1.8
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: rs11708581; hg19: chr3-52428988; COSMIC: COSV70229078; COSMIC: COSV70229078;