rs369627334

Variant names:

• chr16-70818381-G-A
• rs369627334
• NM_001270974.2:c.14619C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_001270974.2(HYDIN):​c.14619C>T​(p.Ile4873Ile) 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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 5

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 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 VariationId is 2646690.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00106 (1549/1461432) while in subpopulation MID AF = 0.00938 (54/5756). AF 95% confidence interval is 0.00738. There are 3 homozygotes in GnomAdExome4. There are 792 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270974.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYDIN	NM_001270974.2	MANE Select	c.14619C>T	p.Ile4873Ile	synonymous	Exon 84 of 86	NP_001257903.1	Q4G0P3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYDIN	ENST00000393567.7	TSL:5 MANE Select	c.14619C>T	p.Ile4873Ile	synonymous	Exon 84 of 86	ENSP00000377197.2	Q4G0P3-1
	HYDIN	ENST00000378856.8	TSL:1	n.*3375C>T		non_coding_transcript_exon	Exon 19 of 22	ENSP00000463350.1	J3QL30
	HYDIN	ENST00000378856.8	TSL:1	n.*3375C>T		3_prime_UTR	Exon 19 of 22	ENSP00000463350.1	J3QL30

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

GnomAD2 exomes AF: 0.000882 AC: 219 AN: 248222 AF XY: 0.00110

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 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

African (AFR) AF: 0.000149 AC: 5 AN: 33468

American (AMR) AF: 0.000604 AC: 27 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26132

East Asian (EAS) AF: 0.00265 AC: 105 AN: 39692

South Asian (SAS) AF: 0.00208 AC: 179 AN: 86160

European-Finnish (FIN) AF: 0.000187 AC: 10 AN: 53382

Middle Eastern (MID) AF: 0.00938 AC: 54 AN: 5756

European-Non Finnish (NFE) AF: 0.000993 AC: 1104 AN: 1111768

Other (OTH) AF: 0.00106 AC: 64 AN: 60376

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

African (AFR) AF: 0.0000722 AC: 3 AN: 41572

American (AMR) AF: 0.000261 AC: 4 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5168

South Asian (SAS) AF: 0.000831 AC: 4 AN: 4814

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10628

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00112 AC: 76 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00112 Hom.: 0

Bravo AF: 0.000672

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	5.8
DANN	Benign	0.43
PhyloP100		4.4
Mutation Taster		=88/12	polymorphism

Splicing

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

Other links and lift over

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