16-70818381-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS1

The NM_001270974.2(HYDIN):c.14619C>T(p.Ile4873=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00102 in 1,613,744 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00066 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0011 (3 hom.)
• Consequence: HYDIN NM_001270974.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.42

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 16-70818381-G-A is Benign according to our data. Variant chr16-70818381-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2646690.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-70818381-G-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000657 (100/152312) while in subpopulation EAS AF= 0.00193 (10/5168). AF 95% confidence interval is 0.00105. There are 0 homozygotes in gnomad4. There are 51 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HYDIN	NM_001270974.2	c.14619C>T	p.Ile4873=	synonymous_variant	84/86	ENST00000393567.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HYDIN	ENST00000393567.7	c.14619C>T	p.Ile4873=	synonymous_variant	84/86	5	NM_001270974.2	P1
HYDIN	ENST00000378856.8	c.*3375C>T		3_prime_UTR_variant, NMD_transcript_variant	19/22	1
HYDIN	ENST00000542283.1	n.113C>T		non_coding_transcript_exon_variant	1/2	5

Frequencies

GnomAD3 genomes AF: 0.000657 AC: 100 AN: 152194 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00112

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000882 AC: 219 AN: 248222 Hom.: 1 AF XY: 0.00110 AC XY: 148 AN XY: 134748

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000406

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00122

Gnomad SAS exome AF: 0.00190

Gnomad FIN exome AF: 0.0000942

Gnomad NFE exome AF: 0.00103

Gnomad OTH exome AF: 0.000995

GnomAD4 exome AF: 0.00106 AC: 1549 AN: 1461432 Hom.: 3 Cov.: 31 AF XY: 0.00109 AC XY: 792 AN XY: 726998

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.000604

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00265

Gnomad4 SAS exome AF: 0.00208

Gnomad4 FIN exome AF: 0.000187

Gnomad4 NFE exome AF: 0.000993

Gnomad4 OTH exome AF: 0.00106

GnomAD4 genome AF: 0.000657 AC: 100 AN: 152312 Hom.: 0 Cov.: 27 AF XY: 0.000685 AC XY: 51 AN XY: 74476

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.000831

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00112

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00112 Hom.: 0

Bravo AF: 0.000672

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2022

HYDIN: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	5.8
Dann	Benign	0.43

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs369627334; hg19: chr16-70852284; COSMIC: COSV101124826;