Variant 16-70818496-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_001270974.2(HYDIN):c.14504T>A(p.Ile4835Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,463,204 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

HYDIN
NM_001270974.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.67

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), HYDIN. . Gene score misZ 0.81019 (greater than the threshold 3.09). Trascript score misZ 4.6175 (greater than threshold 3.09). GenCC has associacion of gene with primary ciliary dyskinesia 5, primary ciliary dyskinesia.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HYDIN	NM_001270974.2 linkuse as main transcript	c.14504T>A	p.Ile4835Asn	missense_variant	84/86	ENST00000393567.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HYDIN	ENST00000393567.7 linkuse as main transcript	c.14504T>A	p.Ile4835Asn	missense_variant	84/86	5	NM_001270974.2	P1	Q4G0P3-1
HYDIN	ENST00000378856.8 linkuse as main transcript	c.*3260T>A		3_prime_UTR_variant, NMD_transcript_variant	19/22	1
HYDIN	ENST00000542283.1 linkuse as main transcript			upstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000270

AC:

AN:

148116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000603

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000114

AC:

AN:

1315088

Hom.:

Cov.:

AF XY:

0.0000122

AC XY:

AN XY:

656730

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000127

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000121

Gnomad4 OTH exome

AF:

0.0000360

GnomAD4 genome

AF:

0.0000270

AC:

AN:

148116

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

71894

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000603

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2021

The c.14504T>A (p.I4835N) alteration is located in exon 84 (coding exon 83) of the HYDIN gene. This alteration results from a T to A substitution at nucleotide position 14504, causing the isoleucine (I) at amino acid position 4835 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.034

MetaRNN

Uncertain

0.72

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

0.60

N;N

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-4.8

REVEL

Benign

0.22

Sift

Uncertain

0.023

Vest4

0.64

MutPred

0.53

Loss of catalytic residue at I4835 (P = 0.0039);

MVP

0.25

ClinPred

0.99

GERP RS

3.6

Varity_R

0.30

gMVP

0.38

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