Variant 16-70809809-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001270974.2(HYDIN):c.14857C>T(p.Arg4953Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00398 in 1,613,950 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0027 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 41 hom. )

Consequence

HYDIN
NM_001270974.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 7.47

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009678125).

BP6

Variant 16-70809809-G-A is Benign according to our data. Variant chr16-70809809-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 445775.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1, Benign=1}. Variant chr16-70809809-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00266 (405/152316) while in subpopulation SAS AF= 0.0166 (80/4816). AF 95% confidence interval is 0.0137. There are 2 homozygotes in gnomad4. There are 207 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HYDIN	NM_001270974.2 link	c.14857C>T	p.Arg4953Trp	missense_variant	85/86	ENST00000393567.7	NP_001257903.1	Q4G0P3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HYDIN	ENST00000393567.7 link	c.14857C>T	p.Arg4953Trp	missense_variant	85/86	5	NM_001270974.2	ENSP00000377197.2	Q4G0P3-1
HYDIN	ENST00000378856.8 link	n.*3737C>T		non_coding_transcript_exon_variant	21/22	1		ENSP00000463350.1	J3QL30
HYDIN	ENST00000378856.8 link	n.*3737C>T		3_prime_UTR_variant	21/22	1		ENSP00000463350.1	J3QL30

Frequencies

GnomAD3 genomes

AF:

0.00267

AC:

406

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00500

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00320

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00426

AC:

1063

AN:

249564

Hom.:

AF XY:

0.00498

AC XY:

674

AN XY:

135396

show subpopulations

Gnomad AFR exome

AF:

0.000904

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.00238

Gnomad EAS exome

AF:

0.00451

Gnomad SAS exome

AF:

0.0147

Gnomad FIN exome

AF:

0.000464

Gnomad NFE exome

AF:

0.00361

Gnomad OTH exome

AF:

0.00363

GnomAD4 exome

AF:

0.00412

AC:

6020

AN:

1461634

Hom.:

Cov.:

AF XY:

0.00450

AC XY:

3273

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.00186

Gnomad4 ASJ exome

AF:

0.00233

Gnomad4 EAS exome

AF:

0.00275

Gnomad4 SAS exome

AF:

0.0153

Gnomad4 FIN exome

AF:

0.000543

Gnomad4 NFE exome

AF:

0.00364

Gnomad4 OTH exome

AF:

0.00489

GnomAD4 genome

AF:

0.00266

AC:

405

AN:

152316

Hom.:

Cov.:

AF XY:

0.00278

AC XY:

207

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00501

Gnomad4 SAS

AF:

0.0166

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00320

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00350

Hom.:

Bravo

AF:

0.00258

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000511

AC:

ESP6500EA

AF:

0.00326

AC:

ExAC

AF:

0.00474

AC:

573

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.00349

EpiControl

AF:

0.00379

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 30, 2017	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2024	HYDIN: BP4, BS1, BS2 -

Primary ciliary dyskinesia 5

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetics and Molecular Pathology, SA Pathology

Oct 03, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.41

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Uncertain

0.96

MetaRNN

Benign

0.0097

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.0

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-6.4

REVEL

Uncertain

0.31

Sift

Uncertain

0.0010

Vest4

0.68

MVP

0.38

ClinPred

0.058

GERP RS

5.9

Varity_R

0.38

gMVP

0.36

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