rs4788770

chr16-71129790-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001270974.2(HYDIN):c.1077T>C(p.Asp359=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,584,486 control chromosomes in the GnomAD database, including 31,086 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (3298 hom., cov: 30)
  • Exomes 𝑓: 0.28 (27788 hom.)
• Consequence: HYDIN NM_001270974.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.70

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-71129790-A-G is Benign according to our data. Variant chr16-71129790-A-G is described in ClinVar as [Benign]. Clinvar id is 402957.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.7 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HYDIN	NM_001270974.2	c.1077T>C	p.Asp359=	synonymous_variant	9/86	ENST00000393567.7
HYDIN	NM_017558.5	c.1077T>C	p.Asp359=	synonymous_variant	9/20
HYDIN	NM_001198542.1	c.1158T>C	p.Asp386=	synonymous_variant	9/19
HYDIN	NM_001198543.1	c.1128T>C	p.Asp376=	synonymous_variant	9/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HYDIN	ENST00000393567.7	c.1077T>C	p.Asp359=	synonymous_variant	9/86	5	NM_001270974.2	P1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 43443 AN: 149160 Hom.: 3287 Cov.: 30

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.284

GnomAD3 exomes AF: 0.336 AC: 71275 AN: 212204 Hom.: 10052 AF XY: 0.329 AC XY: 37756 AN XY: 114780

Gnomad AFR exome AF: 0.305

Gnomad AMR exome AF: 0.525

Gnomad ASJ exome AF: 0.326

Gnomad EAS exome AF: 0.510

Gnomad SAS exome AF: 0.341

Gnomad FIN exome AF: 0.230

Gnomad NFE exome AF: 0.275

Gnomad OTH exome AF: 0.334

GnomAD4 exome AF: 0.277 AC: 397009 AN: 1435208 Hom.: 27788 Cov.: 33 AF XY: 0.278 AC XY: 198395 AN XY: 714000

Gnomad4 AFR exome AF: 0.297

Gnomad4 AMR exome AF: 0.472

Gnomad4 ASJ exome AF: 0.318

Gnomad4 EAS exome AF: 0.457

Gnomad4 SAS exome AF: 0.330

Gnomad4 FIN exome AF: 0.232

Gnomad4 NFE exome AF: 0.258

Gnomad4 OTH exome AF: 0.295

GnomAD4 genome AF: 0.291 AC: 43490 AN: 149278 Hom.: 3298 Cov.: 30 AF XY: 0.291 AC XY: 21226 AN XY: 72862

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.288

Alfa AF: 0.300 Hom.: 779

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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 -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 02, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.31
Dann	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4788770; hg19: chr16-71163693; COSMIC: COSV55476898; COSMIC: COSV55476898;