NM_001270974.2:c.4475C>A

Variant names:

Variant summary

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

The NM_001270974.2(HYDIN):c.4475C>A(p.Pro1492His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.357 in 1,612,908 control chromosomes in the GnomAD database, including 108,409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12231 hom., cov: 29)

Exomes 𝑓: 0.35 ( 96178 hom. )

Consequence

HYDIN
NM_001270974.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 9.30

Publications

19 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=3.117323E-4).

BP6

Variant 16-70981426-G-T is Benign according to our data. Variant chr16-70981426-G-T is described in ClinVar as Benign. ClinVar VariationId is 402956.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYDIN	NM_001270974.2 link	c.4475C>A	p.Pro1492His	missense_variant	Exon 29 of 86	ENST00000393567.7	NP_001257903.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYDIN	ENST00000393567.7 link	c.4475C>A	p.Pro1492His	missense_variant	Exon 29 of 86	5	NM_001270974.2	ENSP00000377197.2

Frequencies

GnomAD3 genomes

AF:

0.392

AC:

59384

AN:

151604

Hom.:

12210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.446

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.517

Gnomad ASJ

AF:

0.400

Gnomad EAS

AF:

0.572

Gnomad SAS

AF:

0.477

Gnomad FIN

AF:

0.283

Gnomad MID

AF:

0.372

Gnomad NFE

AF:

0.329

Gnomad OTH

AF:

0.384

GnomAD2 exomes

AF:

0.415

AC:

102952

AN:

248302

AF XY:

0.408

show subpopulations

Gnomad AFR exome

AF:

0.443

Gnomad AMR exome

AF:

0.635

Gnomad ASJ exome

AF:

0.402

Gnomad EAS exome

AF:

0.567

Gnomad FIN exome

AF:

0.286

Gnomad NFE exome

AF:

0.329

Gnomad OTH exome

AF:

0.396

GnomAD4 exome

AF:

0.354

AC:

516692

AN:

1461182

Hom.:

96178

Cov.:

AF XY:

0.356

AC XY:

259088

AN XY:

726860

show subpopulations

African (AFR)

AF:

0.448

AC:

14974

AN:

33448

American (AMR)

AF:

0.621

AC:

27743

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.405

AC:

10564

AN:

26090

East Asian (EAS)

AF:

0.570

AC:

22610

AN:

39688

South Asian (SAS)

AF:

0.473

AC:

40753

AN:

86166

European-Finnish (FIN)

AF:

0.287

AC:

15311

AN:

53400

Middle Eastern (MID)

AF:

0.367

AC:

2092

AN:

5700

European-Non Finnish (NFE)

AF:

0.324

AC:

360206

AN:

1111678

Other (OTH)

AF:

0.372

AC:

22439

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

17757

35513

53270

71026

88783

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12010

24020

36030

48040

60050

<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:

0.392

AC:

59441

AN:

151726

Hom.:

12231

Cov.:

AF XY:

0.396

AC XY:

29333

AN XY:

74150

show subpopulations

African (AFR)

AF:

0.446

AC:

18425

AN:

41334

American (AMR)

AF:

0.518

AC:

7901

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

1385

AN:

3460

East Asian (EAS)

AF:

0.573

AC:

2945

AN:

5142

South Asian (SAS)

AF:

0.476

AC:

2273

AN:

4776

European-Finnish (FIN)

AF:

0.283

AC:

2986

AN:

10544

Middle Eastern (MID)

AF:

0.380

AC:

111

AN:

292

European-Non Finnish (NFE)

AF:

0.329

AC:

22372

AN:

67914

Other (OTH)

AF:

0.383

AC:

806

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1734

3468

5202

6936

8670

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

584

1168

1752

2336

2920

<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:

0.366

Hom.:

16450

Bravo

AF:

0.414

ExAC

AF:

0.407

AC:

49212

Asia WGS

AF:

0.512

AC:

1781

AN:

3476

EpiCase

AF:

0.344

EpiControl

AF:

0.338

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Primary ciliary dyskinesia 5

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.99

MetaRNN

Benign

0.00031

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.6

PhyloP100

9.3

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-7.1

REVEL

Uncertain

0.32

Sift

Pathogenic

0.0

Vest4

0.34

ClinPred

0.032

GERP RS

4.3

Varity_R

0.76

gMVP

0.70

Mutation Taster

=80/20

polymorphism (auto)

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over