16-71230658-A-G

Variant names:

• chr16-71230658-A-G
• rs3743953
• NM_001270974.2:c.-120T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001270974.2(HYDIN):​c.-120T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,535,720 control chromosomes in the GnomAD database, including 17,121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1845 hom., cov: 32)
  • Exomes 𝑓: 0.13 (15276 hom.)
• Consequence: HYDIN NM_001270974.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.517
• Publications: 15 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, ClinGen, G2P
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000297892 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.80732).
• BP6: Variant 16-71230658-A-G is Benign according to our data. Variant chr16-71230658-A-G is described in ClinVar as Benign. ClinVar VariationId is 402960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYDIN	NM_001270974.2	MANE Select	c.-120T>C		5_prime_UTR	Exon 1 of 86	NP_001257903.1
	HYDIN	NM_001198542.1		c.30T>C	p.Gly10Gly	synonymous	Exon 1 of 19	NP_001185471.1
	HYDIN	NM_017558.5		c.-120T>C		5_prime_UTR	Exon 1 of 20	NP_060028.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYDIN	ENST00000393567.7	TSL:5 MANE Select	c.-120T>C		5_prime_UTR	Exon 1 of 86	ENSP00000377197.2
	HYDIN	ENST00000288168.14	TSL:1	c.28+2T>C		splice_donor intron	N/A	ENSP00000288168.10
	HYDIN	ENST00000538248.5	TSL:2	c.30T>C	p.Gly10Gly	synonymous	Exon 1 of 19	ENSP00000444970.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18576 AN: 151844 Hom.: 1825 Cov.: 32

Gnomad AFR AF: 0.0287

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.0859

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.129

GnomAD2 exomes AF: 0.198 AC: 27062 AN: 136650 AF XY: 0.185

Gnomad AFR exome AF: 0.0252

Gnomad AMR exome AF: 0.474

Gnomad ASJ exome AF: 0.0812

Gnomad EAS exome AF: 0.303

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.116

Gnomad OTH exome AF: 0.164

GnomAD4 exome AF: 0.130 AC: 179822 AN: 1383756 Hom.: 15276 Cov.: 33 AF XY: 0.130 AC XY: 88883 AN XY: 682822

African (AFR) AF: 0.0211 AC: 668 AN: 31594

American (AMR) AF: 0.455 AC: 16237 AN: 35690

Ashkenazi Jewish (ASJ) AF: 0.0811 AC: 2041 AN: 25180

East Asian (EAS) AF: 0.327 AC: 11666 AN: 35728

South Asian (SAS) AF: 0.161 AC: 12747 AN: 79226

European-Finnish (FIN) AF: 0.149 AC: 5035 AN: 33894

Middle Eastern (MID) AF: 0.0878 AC: 500 AN: 5696

European-Non Finnish (NFE) AF: 0.115 AC: 123754 AN: 1078850

Other (OTH) AF: 0.124 AC: 7174 AN: 57898

GnomAD4 genome AF: 0.122 AC: 18606 AN: 151964 Hom.: 1845 Cov.: 32 AF XY: 0.128 AC XY: 9495 AN XY: 74268

African (AFR) AF: 0.0286 AC: 1185 AN: 41450

American (AMR) AF: 0.317 AC: 4833 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0859 AC: 298 AN: 3468

East Asian (EAS) AF: 0.290 AC: 1493 AN: 5146

South Asian (SAS) AF: 0.163 AC: 787 AN: 4814

European-Finnish (FIN) AF: 0.149 AC: 1568 AN: 10548

Middle Eastern (MID) AF: 0.0719 AC: 21 AN: 292

European-Non Finnish (NFE) AF: 0.118 AC: 8020 AN: 67962

Other (OTH) AF: 0.136 AC: 286 AN: 2102

Alfa AF: 0.122 Hom.: 2663

Bravo AF: 0.135

TwinsUK AF: 0.113 AC: 420

ALSPAC AF: 0.117 AC: 451

ExAC AF: 0.106 AC: 1872

Asia WGS AF: 0.239 AC: 829 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in 1000Genomes: 375/2178=17.21%

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.49
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.050	N
PhyloP100		0.52
GERP RS		-0.22
PromoterAI		-0.051	Neutral
Mutation Taster		=297/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3743953; hg19: chr16-71264561; COSMIC: COSV55489429;