3-52375992-G-C

Variant names:

• chr3-52375992-G-C
• rs61738522
• NM_015512.5:c.7197G>C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_015512.5(DNAH1):​c.7197G>C​(p.Val2399Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0024 in 1,612,178 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (55 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (41 hom.)
• Consequence: DNAH1 NM_015512.5 synonymous
• Scores: Splicing: ADA: 0.004131
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.499

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 3-52375992-G-C is Benign according to our data. Variant chr3-52375992-G-C is described in ClinVar as [Benign]. Clinvar id is 478489.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.499 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0131 (2000/152238) while in subpopulation AFR AF= 0.0457 (1896/41514). AF 95% confidence interval is 0.044. There are 55 homozygotes in gnomad4. There are 980 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 55 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH1	NM_015512.5	c.7197G>C	p.Val2399Val	synonymous_variant	Exon 46 of 78	ENST00000420323.7	NP_056327.4
DNAH1	XM_017006129.2	c.7266G>C	p.Val2422Val	synonymous_variant	Exon 48 of 80		XP_016861618.1
DNAH1	XM_017006130.2	c.7197G>C	p.Val2399Val	synonymous_variant	Exon 47 of 79		XP_016861619.1
DNAH1	XM_017006131.2	c.7266G>C	p.Val2422Val	synonymous_variant	Exon 48 of 79		XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH1	ENST00000420323.7	c.7197G>C	p.Val2399Val	synonymous_variant	Exon 46 of 78	1	NM_015512.5	ENSP00000401514.2
DNAH1	ENST00000486752.5	n.7458G>C		non_coding_transcript_exon_variant	Exon 46 of 77	2

Frequencies

GnomAD3 genomes AF: 0.0131 AC: 1995 AN: 152120 Hom.: 55 Cov.: 32

Gnomad AFR AF: 0.0457

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.0101

GnomAD3 exomes AF: 0.00319 AC: 789 AN: 247244 Hom.: 22 AF XY: 0.00232 AC XY: 311 AN XY: 134274

Gnomad AFR exome AF: 0.0461

Gnomad AMR exome AF: 0.00183

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000661

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000711

Gnomad OTH exome AF: 0.00117

GnomAD4 exome AF: 0.00128 AC: 1868 AN: 1459940 Hom.: 41 Cov.: 31 AF XY: 0.00105 AC XY: 764 AN XY: 726254

Gnomad4 AFR exome AF: 0.0464

Gnomad4 AMR exome AF: 0.00197

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000163

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000612

Gnomad4 OTH exome AF: 0.00245

GnomAD4 genome AF: 0.0131 AC: 2000 AN: 152238 Hom.: 55 Cov.: 32 AF XY: 0.0132 AC XY: 980 AN XY: 74456

Gnomad4 AFR AF: 0.0457

Gnomad4 AMR AF: 0.00483

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00995

Alfa AF: 0.000819 Hom.: 2

Bravo AF: 0.0146

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

Sep 16, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Feb 02, 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	-0.49
CADD	Benign	8.2
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0041
dbscSNV1_RF	Benign	0.038
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: rs61738522; hg19: chr3-52410008; COSMIC: COSV99066701; COSMIC: COSV99066701;