Variant 3-52390937-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000420323.7(DNAH1):c.9624C>T(p.Ile3208=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 1,551,744 control chromosomes in the GnomAD database, including 1,481 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 776 hom., cov: 33)

Exomes 𝑓: 0.0093 ( 705 hom. )

Consequence

DNAH1
ENST00000420323.7 splice_region, synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.27

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 3-52390937-C-T is Benign according to our data. Variant chr3-52390937-C-T is described in ClinVar as [Benign]. Clinvar id is 478514.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.27 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DNAH1	NM_015512.5 linkuse as main transcript	c.9624C>T	p.Ile3208=	splice_region_variant, synonymous_variant	61/78	ENST00000420323.7	NP_056327.4
DNAH1	XM_017006129.2 linkuse as main transcript	c.9693C>T	p.Ile3231=	splice_region_variant, synonymous_variant	63/80		XP_016861618.1
DNAH1	XM_017006130.2 linkuse as main transcript	c.9624C>T	p.Ile3208=	splice_region_variant, synonymous_variant	62/79		XP_016861619.1
DNAH1	XM_017006131.2 linkuse as main transcript	c.9567C>T	p.Ile3189=	splice_region_variant, synonymous_variant	62/79		XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH1	ENST00000420323.7 linkuse as main transcript	c.9624C>T	p.Ile3208=	splice_region_variant, synonymous_variant	61/78	1	NM_015512.5	ENSP00000401514	P1	Q9P2D7-4

Frequencies

GnomAD3 genomes

AF:

0.0565

AC:

8595

AN:

152136

Hom.:

772

Cov.:

show subpopulations

Gnomad AFR

AF:

0.189

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00437

Gnomad OTH

AF:

0.0407

GnomAD3 exomes

AF:

0.0154

AC:

2431

AN:

158064

Hom.:

166

AF XY:

0.0137

AC XY:

1139

AN XY:

83304

show subpopulations

Gnomad AFR exome

AF:

0.191

Gnomad AMR exome

AF:

0.00915

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000183

Gnomad SAS exome

AF:

0.0153

Gnomad FIN exome

AF:

0.000472

Gnomad NFE exome

AF:

0.00393

Gnomad OTH exome

AF:

0.00992

GnomAD4 exome

AF:

0.00928

AC:

12983

AN:

1399490

Hom.:

705

Cov.:

AF XY:

0.00895

AC XY:

6181

AN XY:

690238

show subpopulations

Gnomad4 AFR exome

AF:

0.203

Gnomad4 AMR exome

AF:

0.0112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000112

Gnomad4 SAS exome

AF:

0.0153

Gnomad4 FIN exome

AF:

0.000344

Gnomad4 NFE exome

AF:

0.00369

Gnomad4 OTH exome

AF:

0.0157

GnomAD4 genome

AF:

0.0566

AC:

8622

AN:

152254

Hom.:

776

Cov.:

AF XY:

0.0548

AC XY:

4078

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.189

Gnomad4 AMR

AF:

0.0208

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0141

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00437

Gnomad4 OTH

AF:

0.0402

Alfa

AF:

0.0259

Hom.:

159

Bravo

AF:

0.0654

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.25

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over