rs75270082

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001270974.2(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. 14/19 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
NM_001270974.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.158

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 402958.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-71186852-A-G is described in Lovd as [Benign].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYDIN	NM_001270974.2 link	c.44T>C	p.Met15Thr	missense_variant	Exon 2 of 86	ENST00000393567.7	NP_001257903.1	Q4G0P3-1
HYDIN	NM_017558.5 link	c.44T>C	p.Met15Thr	missense_variant	Exon 2 of 20		NP_060028.2	Q4G0P3-5
HYDIN	NM_001198542.1 link	c.125T>C	p.Met42Thr	missense_variant	Exon 2 of 19		NP_001185471.1	Q4G0P3-8
HYDIN	NM_001198543.1 link	c.95T>C	p.Met32Thr	missense_variant	Exon 2 of 19		NP_001185472.1	Q4G0P3-10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYDIN	ENST00000393567.7 link	c.44T>C	p.Met15Thr	missense_variant	Exon 2 of 86	5	NM_001270974.2	ENSP00000377197.2		Q4G0P3-1

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

GnomAD3 exomes

AF:

0.0394

AC:

9884

AN:

250750

Hom.:

290

AF XY:

0.0409

AC XY:

5538

AN XY:

135504

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 SAS exome

AF:

0.0314

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

Gnomad4 AFR exome

AF:

0.0102

Gnomad4 AMR exome

AF:

0.0216

Gnomad4 ASJ exome

AF:

0.0604

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0316

Gnomad4 FIN exome

AF:

0.0311

Gnomad4 NFE exome

AF:

0.0599

Gnomad4 OTH exome

AF:

0.0521

GnomAD4 genome

AF:

0.0387

AC:

5886

AN:

152162

Hom.:

175

Cov.:

AF XY:

0.0373

AC XY:

2774

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0110

Gnomad4 AMR

AF:

0.0376

Gnomad4 ASJ

AF:

0.0582

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0308

Gnomad4 FIN

AF:

0.0286

Gnomad4 NFE

AF:

0.0592

Gnomad4 OTH

AF:

0.0416

Alfa

AF:

0.0531

Hom.:

386

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

Significance: Benign

Submissions summary: Benign:2

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.66

CADD

Benign

9.4

DANN

Benign

0.36

DEOGEN2

Benign

0.035

T;.;.;.;T;.;.

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.034

MetaRNN

Benign

0.0019

T;T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.1

L;L;.;.;.;.;.

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.24

N;N;N;N;N;.;.

REVEL

Benign

0.081

Sift

Benign

0.39

T;T;T;T;T;.;.

Sift4G

Benign

1.0

.;T;T;T;T;.;.

Polyphen

0.0020

.;B;.;.;B;.;.

Vest4

0.37

ClinPred

0.0053

GERP RS

-0.019

Varity_R

0.033

gMVP

0.69

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

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