NM_015512.5:c.3111G>A

Variant names:

• chr3-52353186-G-A
• rs77639782
• NM_015512.5:c.3111G>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.3111G>A​(p.Ser1037Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00761 in 1,613,952 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0080 (67 hom.)
• Consequence: DNAH1 NM_015512.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.74

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=-0.71).
• BP6: Variant 3-52353186-G-A is Benign according to our data. Variant chr3-52353186-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 478438.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-52353186-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-3.74 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00416 (634/152318) while in subpopulation NFE AF= 0.00728 (495/68028). AF 95% confidence interval is 0.00675. There are 0 homozygotes in gnomad4. There are 278 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 67 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH1	NM_015512.5	c.3111G>A	p.Ser1037Ser	synonymous_variant	Exon 19 of 78	ENST00000420323.7	NP_056327.4
DNAH1	XM_017006129.2	c.3111G>A	p.Ser1037Ser	synonymous_variant	Exon 20 of 80		XP_016861618.1
DNAH1	XM_017006130.2	c.3111G>A	p.Ser1037Ser	synonymous_variant	Exon 20 of 79		XP_016861619.1
DNAH1	XM_017006131.2	c.3111G>A	p.Ser1037Ser	synonymous_variant	Exon 20 of 79		XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH1	ENST00000420323.7	c.3111G>A	p.Ser1037Ser	synonymous_variant	Exon 19 of 78	1	NM_015512.5	ENSP00000401514.2
DNAH1	ENST00000486752.5	n.3372G>A		non_coding_transcript_exon_variant	Exon 19 of 77	2
DNAH1	ENST00000497875.1	n.3276G>A		non_coding_transcript_exon_variant	Exon 20 of 21	2

Frequencies

GnomAD3 genomes AF: 0.00417 AC: 635 AN: 152200 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00254

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00728

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00457 AC: 1139 AN: 249108 Hom.: 7 AF XY: 0.00464 AC XY: 627 AN XY: 135170

Gnomad AFR exome AF: 0.00155

Gnomad AMR exome AF: 0.00200

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00291

Gnomad FIN exome AF: 0.00204

Gnomad NFE exome AF: 0.00789

Gnomad OTH exome AF: 0.00364

GnomAD4 exome AF: 0.00797 AC: 11656 AN: 1461634 Hom.: 67 Cov.: 31 AF XY: 0.00787 AC XY: 5722 AN XY: 727106

Gnomad4 AFR exome AF: 0.00108

Gnomad4 AMR exome AF: 0.00190

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00332

Gnomad4 FIN exome AF: 0.00244

Gnomad4 NFE exome AF: 0.00963

Gnomad4 OTH exome AF: 0.00666

GnomAD4 genome AF: 0.00416 AC: 634 AN: 152318 Hom.: 0 Cov.: 33 AF XY: 0.00373 AC XY: 278 AN XY: 74480

Gnomad4 AFR AF: 0.00135

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.00254

Gnomad4 NFE AF: 0.00728

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00523 Hom.: 1

Bravo AF: 0.00414

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00692

EpiControl AF: 0.00771

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DNAH1: BP4, BP7, BS2 -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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	-0.71
CADD	Benign	0.19
DANN	Benign	0.80

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: rs77639782; hg19: chr3-52387202;