16-70828356-T-C

Variant names:

• chr16-70828356-T-C
• rs888154119
• NM_001270974.2:c.14186A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001270974.2(HYDIN):​c.14186A>G​(p.Lys4729Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 21)
  • Exomes 𝑓: 0.0000012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HYDIN NM_001270974.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.20
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13334668).

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.14186A>G	p.Lys4729Arg	missense	Exon 82 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.14186A>G	p.Lys4729Arg	missense	Exon 82 of 86	ENSP00000377197.2	Q4G0P3-1
	HYDIN	ENST00000378856.8	TSL:1	n.*2942A>G		non_coding_transcript_exon	Exon 17 of 22	ENSP00000463350.1	J3QL30
	HYDIN	ENST00000378856.8	TSL:1	n.*2942A>G		3_prime_UTR	Exon 17 of 22	ENSP00000463350.1	J3QL30

Frequencies

GnomAD3 genomes AF: 0.0000136 AC: 2 AN: 146712 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.0000509

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000122 AC: 1 AN: 819900 Hom.: 0 Cov.: 11 AF XY: 0.00000233 AC XY: 1 AN XY: 429908

African (AFR) AF: 0.00 AC: 0 AN: 20146

American (AMR) AF: 0.00 AC: 0 AN: 32202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20830

East Asian (EAS) AF: 0.00 AC: 0 AN: 35312

South Asian (SAS) AF: 0.00 AC: 0 AN: 67294

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49730

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4202

European-Non Finnish (NFE) AF: 0.00000181 AC: 1 AN: 551326

Other (OTH) AF: 0.00 AC: 0 AN: 38858

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000136 AC: 2 AN: 146712 Hom.: 0 Cov.: 21 AF XY: 0.0000140 AC XY: 1 AN XY: 71218

African (AFR) AF: 0.0000509 AC: 2 AN: 39304

American (AMR) AF: 0.00 AC: 0 AN: 14654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3410

East Asian (EAS) AF: 0.00 AC: 0 AN: 4960

South Asian (SAS) AF: 0.00 AC: 0 AN: 4442

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66564

Other (OTH) AF: 0.00 AC: 0 AN: 1994

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.85	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.3	L
PhyloP100		3.2
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.098
Sift	Benign	0.15	T
Vest4		0.23
MutPred		0.38		Loss of ubiquitination at K4729 (P = 0.0326)
MVP		0.16
ClinPred		0.85	D
GERP RS		4.2
Varity_R		0.091
gMVP		0.074
Mutation Taster		=96/4	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs888154119; hg19: chr16-70862259;