16-70981426-G-T

Variant names:

• chr16-70981426-G-T
• rs78763837
• NM_001270974.2:c.4475C>A

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.4475C>A​(p.Pro1492His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.357 in 1,612,908 control chromosomes in the GnomAD database, including 108,409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12231 hom., cov: 29)
  • Exomes 𝑓: 0.35 (96178 hom.)
• Consequence: HYDIN NM_001270974.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 9.30

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

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

• BP4: Computational evidence support a benign effect (MetaRNN=3.117323E-4).
• BP6: Variant 16-70981426-G-T is Benign according to our data. Variant chr16-70981426-G-T is described in ClinVar as [Benign]. Clinvar id is 402956.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYDIN	NM_001270974.2	c.4475C>A	p.Pro1492His	missense_variant	Exon 29 of 86	ENST00000393567.7	NP_001257903.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYDIN	ENST00000393567.7	c.4475C>A	p.Pro1492His	missense_variant	Exon 29 of 86	5	NM_001270974.2	ENSP00000377197.2

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59384 AN: 151604 Hom.: 12210 Cov.: 29

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.372

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.384

GnomAD2 exomes AF: 0.415 AC: 102952 AN: 248302 AF XY: 0.408

Gnomad AFR exome AF: 0.443

Gnomad AMR exome AF: 0.635

Gnomad ASJ exome AF: 0.402

Gnomad EAS exome AF: 0.567

Gnomad FIN exome AF: 0.286

Gnomad NFE exome AF: 0.329

Gnomad OTH exome AF: 0.396

GnomAD4 exome AF: 0.354 AC: 516692 AN: 1461182 Hom.: 96178 Cov.: 37 AF XY: 0.356 AC XY: 259088 AN XY: 726860

Gnomad4 AFR exome AF: 0.448 AC: 14974 AN: 33448

Gnomad4 AMR exome AF: 0.621 AC: 27743 AN: 44652

Gnomad4 ASJ exome AF: 0.405 AC: 10564 AN: 26090

Gnomad4 EAS exome AF: 0.570 AC: 22610 AN: 39688

Gnomad4 SAS exome AF: 0.473 AC: 40753 AN: 86166

Gnomad4 FIN exome AF: 0.287 AC: 15311 AN: 53400

Gnomad4 NFE exome AF: 0.324 AC: 360206 AN: 1111678

Gnomad4 Remaining exome AF: 0.372 AC: 22439 AN: 60360

GnomAD4 genome AF: 0.392 AC: 59441 AN: 151726 Hom.: 12231 Cov.: 29 AF XY: 0.396 AC XY: 29333 AN XY: 74150

Gnomad4 AFR AF: 0.446 AC: 0.445759 AN: 0.445759

Gnomad4 AMR AF: 0.518 AC: 0.518166 AN: 0.518166

Gnomad4 ASJ AF: 0.400 AC: 0.400289 AN: 0.400289

Gnomad4 EAS AF: 0.573 AC: 0.572734 AN: 0.572734

Gnomad4 SAS AF: 0.476 AC: 0.475921 AN: 0.475921

Gnomad4 FIN AF: 0.283 AC: 0.283194 AN: 0.283194

Gnomad4 NFE AF: 0.329 AC: 0.329417 AN: 0.329417

Gnomad4 OTH AF: 0.383 AC: 0.382716 AN: 0.382716

Alfa AF: 0.366 Hom.: 16450

Bravo AF: 0.414

ExAC AF: 0.407 AC: 49212

Asia WGS AF: 0.512 AC: 1781 AN: 3476

EpiCase AF: 0.344

EpiControl AF: 0.338

ClinVar

Significance: Benign

Submissions summary: Benign:3

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 -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Primary ciliary dyskinesia 5 Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
MetaRNN	Benign	0.00031	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-7.1	D
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D
Vest4		0.34
ClinPred		0.032	T
GERP RS		4.3
Varity_R		0.76
gMVP		0.70
Mutation Taster		=80/20	polymorphism (auto)

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs78763837; hg19: chr16-71015329; COSMIC: COSV66829426; COSMIC: COSV66829426;