rs11714402

Variant names:

• chr3-52357719-A-C
• rs11714402
• NM_015512.5:c.3964A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-52357719-A-C
• chr3-52357719-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015512.5(DNAH1):​c.3964A>C​(p.Arg1322Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,579,880 control chromosomes in the GnomAD database, including 24,980 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2849 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22131 hom.)
• Consequence: DNAH1 NM_015512.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.257
• Publications: 17 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: Labcorp Genetics (formerly Invitae), ClinGen
• ciliary dyskinesia, primary, 37

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 3-52357719-A-C is Benign according to our data. Variant chr3-52357719-A-C is described in ClinVar as Benign. ClinVar VariationId is 402598.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.257 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015512.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH1	NM_015512.5	MANE Select	c.3964A>C	p.Arg1322Arg	synonymous	Exon 23 of 78	NP_056327.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH1	ENST00000420323.7	TSL:1 MANE Select	c.3964A>C	p.Arg1322Arg	synonymous	Exon 23 of 78	ENSP00000401514.2	Q9P2D7-4
	DNAH1	ENST00000486752.5	TSL:2	n.4225A>C		non_coding_transcript_exon	Exon 23 of 77

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27791 AN: 152056 Hom.: 2845 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0271

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0846

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.196

GnomAD2 exomes AF: 0.139 AC: 27039 AN: 194792 AF XY: 0.137

Gnomad AFR exome AF: 0.254

Gnomad AMR exome AF: 0.113

Gnomad ASJ exome AF: 0.154

Gnomad EAS exome AF: 0.0207

Gnomad FIN exome AF: 0.0889

Gnomad NFE exome AF: 0.169

Gnomad OTH exome AF: 0.148

GnomAD4 exome AF: 0.171 AC: 243798 AN: 1427706 Hom.: 22131 Cov.: 33 AF XY: 0.169 AC XY: 119265 AN XY: 707098

African (AFR) AF: 0.269 AC: 8790 AN: 32682

American (AMR) AF: 0.121 AC: 4788 AN: 39620

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 3967 AN: 25516

East Asian (EAS) AF: 0.0201 AC: 763 AN: 37952

South Asian (SAS) AF: 0.119 AC: 9778 AN: 82066

European-Finnish (FIN) AF: 0.0936 AC: 4722 AN: 50466

Middle Eastern (MID) AF: 0.154 AC: 884 AN: 5732

European-Non Finnish (NFE) AF: 0.183 AC: 199757 AN: 1094506

Other (OTH) AF: 0.175 AC: 10349 AN: 59166

GnomAD4 genome AF: 0.183 AC: 27811 AN: 152174 Hom.: 2849 Cov.: 32 AF XY: 0.176 AC XY: 13086 AN XY: 74414

African (AFR) AF: 0.258 AC: 10722 AN: 41496

American (AMR) AF: 0.152 AC: 2321 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 558 AN: 3468

East Asian (EAS) AF: 0.0268 AC: 139 AN: 5186

South Asian (SAS) AF: 0.112 AC: 539 AN: 4818

European-Finnish (FIN) AF: 0.0846 AC: 898 AN: 10612

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12022 AN: 67992

Other (OTH) AF: 0.197 AC: 416 AN: 2112

Alfa AF: 0.180 Hom.: 4204

Bravo AF: 0.190

Asia WGS AF: 0.0890 AC: 312 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	6.2
DANN	Benign	0.40
PhyloP100		0.26
Mutation Taster		=99/1	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: rs11714402; hg19: chr3-52391735; COSMIC: COSV70229072; COSMIC: COSV70229072;