rs75270082

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000393567.7(HYDIN):c.44T>C(p.Met15Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0515 in 1,612,828 control chromosomes in the GnomAD database, including 2,516 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 175 hom., cov: 32)

Exomes 𝑓: 0.053 ( 2341 hom. )

Consequence

HYDIN
ENST00000393567.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.158

Publications

12 publications found

Variant links:

Genes affected

HYDIN (HGNC:19368): (HYDIN axonemal central pair apparatus protein) This gene encodes a protein that may be involved in cilia motility. Mutations in this gene cause of autosomal recessive primary ciliary dyskinesia-5, a disorder characterized by the accumulation of cerebrospinal fluid within the ventricles of the brain. A duplicate copy of this gene has been found in humans on chromosome 1. [provided by RefSeq, Jan 2013]

HYDIN Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 5
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, ClinGen, G2P
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

HYDIN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019213855).

BP6

Variant 16-71186852-A-G is Benign according to our data. Variant chr16-71186852-A-G is described in ClinVar as Benign. ClinVar VariationId is 402958.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0577 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000393567.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
HYDIN	NM_001270974.2	MANE Select	c.44T>C	p.Met15Thr	missense	Exon 2 of 86	NP_001257903.1
HYDIN	NM_017558.5		c.44T>C	p.Met15Thr	missense	Exon 2 of 20	NP_060028.2
HYDIN	NM_001198542.1		c.125T>C	p.Met42Thr	missense	Exon 2 of 19	NP_001185471.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
HYDIN	ENST00000393567.7	TSL:5 MANE Select	c.44T>C	p.Met15Thr	missense	Exon 2 of 86	ENSP00000377197.2
HYDIN	ENST00000288168.14	TSL:1	c.95T>C	p.Met32Thr	missense	Exon 2 of 15	ENSP00000288168.10
HYDIN	ENST00000321489.9	TSL:2	c.44T>C	p.Met15Thr	missense	Exon 2 of 20	ENSP00000314736.5

Frequencies

GnomAD3 genomes

AF:

0.0387

AC:

5883

AN:

152044

Hom.:

175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0111

Gnomad AMI

AF:

0.0824

Gnomad AMR

AF:

0.0376

Gnomad ASJ

AF:

0.0582

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0303

Gnomad FIN

AF:

0.0286

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0592

Gnomad OTH

AF:

0.0420

GnomAD2 exomes

AF:

0.0394

AC:

9884

AN:

250750

AF XY:

0.0409

show subpopulations

Gnomad AFR exome

AF:

0.0120

Gnomad AMR exome

AF:

0.0197

Gnomad ASJ exome

AF:

0.0593

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0281

Gnomad NFE exome

AF:

0.0578

Gnomad OTH exome

AF:

0.0499

GnomAD4 exome

AF:

0.0529

AC:

77236

AN:

1460666

Hom.:

2341

Cov.:

AF XY:

0.0526

AC XY:

38195

AN XY:

726698

show subpopulations

African (AFR)

AF:

0.0102

AC:

341

AN:

33450

American (AMR)

AF:

0.0216

AC:

965

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0604

AC:

1577

AN:

26114

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39676

South Asian (SAS)

AF:

0.0316

AC:

2726

AN:

86186

European-Finnish (FIN)

AF:

0.0311

AC:

1661

AN:

53406

Middle Eastern (MID)

AF:

0.0446

AC:

257

AN:

5762

European-Non Finnish (NFE)

AF:

0.0599

AC:

66559

AN:

1110998

Other (OTH)

AF:

0.0521

AC:

3147

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

3309

6619

9928

13238

16547

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2434

4868

7302

9736

12170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0387

AC:

5886

AN:

152162

Hom.:

175

Cov.:

AF XY:

0.0373

AC XY:

2774

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.0110

AC:

458

AN:

41546

American (AMR)

AF:

0.0376

AC:

574

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.0582

AC:

202

AN:

3472

East Asian (EAS)

AF:

0.000194

AC:

AN:

5166

South Asian (SAS)

AF:

0.0308

AC:

148

AN:

4812

European-Finnish (FIN)

AF:

0.0286

AC:

303

AN:

10596

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0592

AC:

4023

AN:

67982

Other (OTH)

AF:

0.0416

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

283

566

849

1132

1415

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0511

Hom.:

784

Bravo

AF:

0.0378

TwinsUK

AF:

0.0569

AC:

211

ALSPAC

AF:

0.0553

AC:

213

ESP6500AA

AF:

0.00978

AC:

ESP6500EA

AF:

0.0601

AC:

517

ExAC

AF:

0.0411

AC:

4986

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0619

EpiControl

AF:

0.0563

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.66

CADD

Benign

9.4

(source)

DANN

Benign

0.36

DEOGEN2

Benign

0.035

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.034

MetaRNN

Benign

0.0019

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.1

PhyloP100

0.16

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.24

REVEL

Benign

0.081

Sift

Benign

0.39

Sift4G

Benign

1.0

Polyphen

0.0020

Vest4

0.37

ClinPred

0.0053

GERP RS

-0.019

Varity_R

0.033

gMVP

0.69

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over