rs113529103

Positions:

• chr3-52382362-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015512.5(DNAH1):​c.7848C>T​(p.Tyr2616=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00361 in 1,613,994 control chromosomes in the GnomAD database, including 174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (74 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (100 hom.)
• Consequence: DNAH1 NM_015512.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.40

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=-0.63).
• BP6: Variant 3-52382362-C-T is Benign according to our data. Variant chr3-52382362-C-T is described in ClinVar as [Benign]. Clinvar id is 478495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.39 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH1	NM_015512.5	c.7848C>T	p.Tyr2616=	synonymous_variant	50/78	ENST00000420323.7
DNAH1	XM_017006129.2	c.7917C>T	p.Tyr2639=	synonymous_variant	52/80
DNAH1	XM_017006130.2	c.7848C>T	p.Tyr2616=	synonymous_variant	51/79
DNAH1	XM_017006131.2	c.7917C>T	p.Tyr2639=	synonymous_variant	52/79

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH1	ENST00000420323.7	c.7848C>T	p.Tyr2616=	synonymous_variant	50/78	1	NM_015512.5	P1
DNAH1	ENST00000486752.5	n.8109C>T		non_coding_transcript_exon_variant	50/77	2

Frequencies

GnomAD3 genomes AF: 0.0184 AC: 2801 AN: 152184 Hom.: 74 Cov.: 33

Gnomad AFR AF: 0.0634

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.00485 AC: 1210 AN: 249244 Hom.: 37 AF XY: 0.00399 AC XY: 539 AN XY: 135214

Gnomad AFR exome AF: 0.0679

Gnomad AMR exome AF: 0.00284

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.000464

Gnomad NFE exome AF: 0.000310

Gnomad OTH exome AF: 0.00182

GnomAD4 exome AF: 0.00207 AC: 3026 AN: 1461692 Hom.: 100 Cov.: 32 AF XY: 0.00181 AC XY: 1316 AN XY: 727134

Gnomad4 AFR exome AF: 0.0703

Gnomad4 AMR exome AF: 0.00367

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.000393

Gnomad4 NFE exome AF: 0.000179

Gnomad4 OTH exome AF: 0.00441

GnomAD4 genome AF: 0.0184 AC: 2805 AN: 152302 Hom.: 74 Cov.: 33 AF XY: 0.0180 AC XY: 1338 AN XY: 74474

Gnomad4 AFR AF: 0.0633

Gnomad4 AMR AF: 0.00849

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.00992

Alfa AF: 0.00793 Hom.: 20

Bravo AF: 0.0220

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 16, 2023	- -

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.12
DANN	Benign	0.27

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs113529103; hg19: chr3-52416378;