Variant 3-52326295-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_015512.5(DNAH1):c.562C>T(p.Arg188Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,608,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

DNAH1
NM_015512.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.98

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:

DNAH1 (HGNC:):

DNAH1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.85

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH1	NM_015512.5 linkuse as main transcript	c.562C>T	p.Arg188Cys	missense_variant	4/78	ENST00000420323.7	NP_056327.4	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006129.2 linkuse as main transcript	c.562C>T	p.Arg188Cys	missense_variant	5/80		XP_016861618.1
DNAH1	XM_017006130.2 linkuse as main transcript	c.562C>T	p.Arg188Cys	missense_variant	5/79		XP_016861619.1	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006131.2 linkuse as main transcript	c.562C>T	p.Arg188Cys	missense_variant	5/79		XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNAH1	ENST00000420323.7 linkuse as main transcript	c.562C>T	p.Arg188Cys	missense_variant	4/78	1	NM_015512.5	ENSP00000401514.2	Q9P2D7-4
DNAH1	ENST00000486752.5 linkuse as main transcript	n.823C>T		non_coding_transcript_exon_variant	4/77	2
DNAH1	ENST00000497875.1 linkuse as main transcript	n.727C>T		non_coding_transcript_exon_variant	5/21	2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00000892

AC:

AN:

1456618

Hom.:

Cov.:

AF XY:

0.00000690

AC XY:

AN XY:

724758

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000453

ExAC

AF:

0.00000826

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Uncertain

0.084

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Pathogenic

1.0

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.059

MetaRNN

Pathogenic

0.85

MetaSVM

Benign

-0.56

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-5.6

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Vest4

0.80

MutPred

0.67

Loss of disorder (P = 0.0136);

MVP

0.52

MPC

0.68

ClinPred

1.0

GERP RS

5.0

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over