chr3-52392868-C-T

Variant names:

• chr3-52392868-C-T
• rs419050
• NM_015512.5:c.10317C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_015512.5(DNAH1):​c.10317C>T​(p.Ile3439Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0446 in 1,608,620 control chromosomes in the GnomAD database, including 1,787 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (141 hom., cov: 30)
  • Exomes 𝑓: 0.045 (1646 hom.)
• Consequence: DNAH1 NM_015512.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.67

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 3-52392868-C-T is Benign according to our data. Variant chr3-52392868-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 478382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0381 (5666/148804) while in subpopulation NFE AF= 0.0494 (3323/67324). AF 95% confidence interval is 0.048. There are 141 homozygotes in gnomad4. There are 2595 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 141 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH1	NM_015512.5	c.10317C>T	p.Ile3439Ile	synonymous_variant	Exon 65 of 78	ENST00000420323.7	NP_056327.4
DNAH1	XM_017006129.2	c.10386C>T	p.Ile3462Ile	synonymous_variant	Exon 67 of 80		XP_016861618.1
DNAH1	XM_017006130.2	c.10317C>T	p.Ile3439Ile	synonymous_variant	Exon 66 of 79		XP_016861619.1
DNAH1	XM_017006131.2	c.10260C>T	p.Ile3420Ile	synonymous_variant	Exon 66 of 79		XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH1	ENST00000420323.7	c.10317C>T	p.Ile3439Ile	synonymous_variant	Exon 65 of 78	1	NM_015512.5	ENSP00000401514.2
DNAH1	ENST00000486752.5	n.10774C>T		non_coding_transcript_exon_variant	Exon 64 of 77	2
DNAH1	ENST00000488988.5	n.2103C>T		non_coding_transcript_exon_variant	Exon 12 of 25	2
DNAH1	ENST00000490713.5	n.1017C>T		non_coding_transcript_exon_variant	Exon 8 of 20	5		ENSP00000419071.1

Frequencies

GnomAD3 genomes AF: 0.0381 AC: 5665 AN: 148688 Hom.: 140 Cov.: 30

Gnomad AFR AF: 0.0206

Gnomad AMI AF: 0.0837

Gnomad AMR AF: 0.0487

Gnomad ASJ AF: 0.0298

Gnomad EAS AF: 0.0208

Gnomad SAS AF: 0.0216

Gnomad FIN AF: 0.0310

Gnomad MID AF: 0.0387

Gnomad NFE AF: 0.0494

Gnomad OTH AF: 0.0432

GnomAD3 exomes AF: 0.0373 AC: 9259 AN: 248252 Hom.: 217 AF XY: 0.0375 AC XY: 5054 AN XY: 134748

Gnomad AFR exome AF: 0.0218

Gnomad AMR exome AF: 0.0340

Gnomad ASJ exome AF: 0.0289

Gnomad EAS exome AF: 0.0178

Gnomad SAS exome AF: 0.0193

Gnomad FIN exome AF: 0.0322

Gnomad NFE exome AF: 0.0497

Gnomad OTH exome AF: 0.0472

GnomAD4 exome AF: 0.0453 AC: 66152 AN: 1459816 Hom.: 1646 Cov.: 40 AF XY: 0.0449 AC XY: 32611 AN XY: 726106

Gnomad4 AFR exome AF: 0.0230

Gnomad4 AMR exome AF: 0.0369

Gnomad4 ASJ exome AF: 0.0300

Gnomad4 EAS exome AF: 0.0167

Gnomad4 SAS exome AF: 0.0198

Gnomad4 FIN exome AF: 0.0334

Gnomad4 NFE exome AF: 0.0502

Gnomad4 OTH exome AF: 0.0466

GnomAD4 genome AF: 0.0381 AC: 5666 AN: 148804 Hom.: 141 Cov.: 30 AF XY: 0.0359 AC XY: 2595 AN XY: 72374

Gnomad4 AFR AF: 0.0205

Gnomad4 AMR AF: 0.0487

Gnomad4 ASJ AF: 0.0298

Gnomad4 EAS AF: 0.0204

Gnomad4 SAS AF: 0.0214

Gnomad4 FIN AF: 0.0310

Gnomad4 NFE AF: 0.0494

Gnomad4 OTH AF: 0.0451

Alfa AF: 0.0486 Hom.: 254

Bravo AF: 0.0395

Asia WGS AF: 0.0360 AC: 123 AN: 3478

EpiCase AF: 0.0501

EpiControl AF: 0.0544

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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	-0.61
CADD	Benign	1.4
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs419050; hg19: chr3-52426884;