Variant 16-70981426-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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=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 id 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	Q4G0P3-1

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		Q4G0P3-1

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

GnomAD3 exomes

AF:

0.415

AC:

102952

AN:

248302

Hom.:

23178

AF XY:

0.408

AC XY:

54928

AN XY:

134702

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 SAS exome

AF:

0.477

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

Gnomad4 AFR exome

AF:

0.448

Gnomad4 AMR exome

AF:

0.621

Gnomad4 ASJ exome

AF:

0.405

Gnomad4 EAS exome

AF:

0.570

Gnomad4 SAS exome

AF:

0.473

Gnomad4 FIN exome

AF:

0.287

Gnomad4 NFE exome

AF:

0.324

Gnomad4 OTH exome

AF:

0.372

GnomAD4 genome

AF:

0.392

AC:

59441

AN:

151726

Hom.:

12231

Cov.:

AF XY:

0.396

AC XY:

29333

AN XY:

74150

show subpopulations

Gnomad4 AFR

AF:

0.446

Gnomad4 AMR

AF:

0.518

Gnomad4 ASJ

AF:

0.400

Gnomad4 EAS

AF:

0.573

Gnomad4 SAS

AF:

0.476

Gnomad4 FIN

AF:

0.283

Gnomad4 NFE

AF:

0.329

Gnomad4 OTH

AF:

0.383

Alfa

AF:

0.353

Hom.:

8067

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

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Primary ciliary dyskinesia 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

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

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

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

Splicing

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