rs369578432

Variant names:

• chr3-52361727-G-A
• rs369578432
• NM_015512.5:c.4941G>A

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.4941G>A​(p.Ala1647Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 1,610,794 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (2 hom.)
• Consequence: DNAH1 NM_015512.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -8.06

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=-0.67).
• BP6: Variant 3-52361727-G-A is Benign according to our data. Variant chr3-52361727-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 478452.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-8.06 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00113 (172/152346) while in subpopulation NFE AF= 0.00215 (146/68036). AF 95% confidence interval is 0.00186. There are 1 homozygotes in gnomad4. There are 72 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH1	NM_015512.5	c.4941G>A	p.Ala1647Ala	synonymous_variant	Exon 30 of 78	ENST00000420323.7	NP_056327.4
DNAH1	XM_017006129.2	c.4941G>A	p.Ala1647Ala	synonymous_variant	Exon 31 of 80		XP_016861618.1
DNAH1	XM_017006130.2	c.4941G>A	p.Ala1647Ala	synonymous_variant	Exon 31 of 79		XP_016861619.1
DNAH1	XM_017006131.2	c.4941G>A	p.Ala1647Ala	synonymous_variant	Exon 31 of 79		XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH1	ENST00000420323.7	c.4941G>A	p.Ala1647Ala	synonymous_variant	Exon 30 of 78	1	NM_015512.5	ENSP00000401514.2
DNAH1	ENST00000486752.5	n.5202G>A		non_coding_transcript_exon_variant	Exon 30 of 77	2
DNAH1	ENST00000466628.1	n.134+375G>A		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.00113 AC: 172 AN: 152228 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00215

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000764 AC: 185 AN: 242230 Hom.: 0 AF XY: 0.000752 AC XY: 99 AN XY: 131678

Gnomad AFR exome AF: 0.000204

Gnomad AMR exome AF: 0.000177

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000169

Gnomad FIN exome AF: 0.000332

Gnomad NFE exome AF: 0.00147

Gnomad OTH exome AF: 0.000508

GnomAD4 exome AF: 0.00162 AC: 2362 AN: 1458448 Hom.: 2 Cov.: 32 AF XY: 0.00149 AC XY: 1078 AN XY: 725176

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.000158

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000585

Gnomad4 FIN exome AF: 0.000454

Gnomad4 NFE exome AF: 0.00203

Gnomad4 OTH exome AF: 0.000946

GnomAD4 genome AF: 0.00113 AC: 172 AN: 152346 Hom.: 1 Cov.: 33 AF XY: 0.000966 AC XY: 72 AN XY: 74496

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.00215

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00146 Hom.: 0

Bravo AF: 0.000971

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Benign:2

Feb 24, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely 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	-0.67
CADD	Benign	0.12
DANN	Benign	0.81

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: rs369578432; hg19: chr3-52395743;