3-52347854-C-T

Variant names:

• chr3-52347854-C-T
• rs376991251
• NM_015512.5:c.1986C>T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_015512.5(DNAH1):​c.1986C>T​(p.Asp662Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0015 in 1,600,494 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (22 hom.)
• Consequence: DNAH1 NM_015512.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.574

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 3-52347854-C-T is Benign according to our data. Variant chr3-52347854-C-T is described in ClinVar as [Benign]. Clinvar id is 478422.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.574 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00106 (161/152304) while in subpopulation SAS AF= 0.0135 (65/4830). AF 95% confidence interval is 0.0108. There are 0 homozygotes in gnomad4. There are 95 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH1	NM_015512.5	c.1986C>T	p.Asp662Asp	synonymous_variant	Exon 12 of 78	ENST00000420323.7	NP_056327.4
DNAH1	XM_017006129.2	c.1986C>T	p.Asp662Asp	synonymous_variant	Exon 13 of 80		XP_016861618.1
DNAH1	XM_017006130.2	c.1986C>T	p.Asp662Asp	synonymous_variant	Exon 13 of 79		XP_016861619.1
DNAH1	XM_017006131.2	c.1986C>T	p.Asp662Asp	synonymous_variant	Exon 13 of 79		XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH1	ENST00000420323.7	c.1986C>T	p.Asp662Asp	synonymous_variant	Exon 12 of 78	1	NM_015512.5	ENSP00000401514.2
DNAH1	ENST00000486752.5	n.2247C>T		non_coding_transcript_exon_variant	Exon 12 of 77	2
DNAH1	ENST00000497875.1	n.2151C>T		non_coding_transcript_exon_variant	Exon 13 of 21	2

Frequencies

GnomAD3 genomes AF: 0.00106 AC: 161 AN: 152186 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0134

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00107

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00231 AC: 529 AN: 229476 Hom.: 4 AF XY: 0.00304 AC XY: 378 AN XY: 124224

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000248

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0129

Gnomad FIN exome AF: 0.000488

Gnomad NFE exome AF: 0.00140

Gnomad OTH exome AF: 0.00106

GnomAD4 exome AF: 0.00154 AC: 2237 AN: 1448190 Hom.: 22 Cov.: 31 AF XY: 0.00194 AC XY: 1391 AN XY: 718790

Gnomad4 AFR exome AF: 0.0000602

Gnomad4 AMR exome AF: 0.000350

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0135

Gnomad4 FIN exome AF: 0.000398

Gnomad4 NFE exome AF: 0.000834

Gnomad4 OTH exome AF: 0.00192

GnomAD4 genome AF: 0.00106 AC: 161 AN: 152304 Hom.: 0 Cov.: 33 AF XY: 0.00128 AC XY: 95 AN XY: 74478

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000785

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0135

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.00107

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000808 Hom.: 0

Bravo AF: 0.000805

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	9.3
DANN	Benign	0.89

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: rs376991251; hg19: chr3-52381870;