3-52368747-C-T

Variant names:

• chr3-52368747-C-T
• rs187752630
• NM_015512.5:c.5772C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_015512.5(DNAH1):​c.5772C>T​(p.Asp1924Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,613,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: DNAH1 NM_015512.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.628
• Publications: 1 publications found

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]

DNAH1 Gene-Disease associations (from GenCC):

• spermatogenic failure 18

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• ciliary dyskinesia, primary, 37

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 3-52368747-C-T is Benign according to our data. Variant chr3-52368747-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 478465.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.628 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH1	NM_015512.5	c.5772C>T	p.Asp1924Asp	synonymous_variant	Exon 37 of 78	ENST00000420323.7	NP_056327.4
DNAH1	XM_017006129.2	c.5841C>T	p.Asp1947Asp	synonymous_variant	Exon 39 of 80		XP_016861618.1
DNAH1	XM_017006130.2	c.5772C>T	p.Asp1924Asp	synonymous_variant	Exon 38 of 79		XP_016861619.1
DNAH1	XM_017006131.2	c.5841C>T	p.Asp1947Asp	synonymous_variant	Exon 39 of 79		XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH1	ENST00000420323.7	c.5772C>T	p.Asp1924Asp	synonymous_variant	Exon 37 of 78	1	NM_015512.5	ENSP00000401514.2
DNAH1	ENST00000486752.5	n.6033C>T		non_coding_transcript_exon_variant	Exon 37 of 77	2

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000141 AC: 35 AN: 248892 AF XY: 0.000148

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.000493

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000111

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.000122 AC: 178 AN: 1460996 Hom.: 0 Cov.: 31 AF XY: 0.000113 AC XY: 82 AN XY: 726776

African (AFR) AF: 0.0000299 AC: 1 AN: 33464

American (AMR) AF: 0.000403 AC: 18 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86226

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5446

European-Non Finnish (NFE) AF: 0.000137 AC: 152 AN: 1111688

Other (OTH) AF: 0.0000497 AC: 3 AN: 60310

GnomAD4 genome AF: 0.0000853 AC: 13 AN: 152318 Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6 AN XY: 74476

African (AFR) AF: 0.0000481 AC: 2 AN: 41570

American (AMR) AF: 0.000131 AC: 2 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000112 Hom.: 0

Bravo AF: 0.000125

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Dec 08, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely 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	-0.50
CADD	Benign	2.3
DANN	Benign	0.87
PhyloP100		-0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs187752630; hg19: chr3-52402763; COSMIC: COSV70236520; COSMIC: COSV70236520;