chr16-71129790-A-G

Variant names:

• chr16-71129790-A-G
• rs4788770
• NM_001270974.2:c.1077T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001270974.2(HYDIN):​c.1077T>C​(p.Asp359Asp) 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:3
• Conservation: PhyloP100: -1.70
• Publications: 11 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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.1077T>C	p.Asp359Asp	synonymous	Exon 9 of 86	NP_001257903.1
	HYDIN	NM_017558.5		c.1077T>C	p.Asp359Asp	synonymous	Exon 9 of 20	NP_060028.2
	HYDIN	NM_001198542.1		c.1158T>C	p.Asp386Asp	synonymous	Exon 9 of 19	NP_001185471.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYDIN	ENST00000393567.7	TSL:5 MANE Select	c.1077T>C	p.Asp359Asp	synonymous	Exon 9 of 86	ENSP00000377197.2
	HYDIN	ENST00000288168.14	TSL:1	c.1128T>C	p.Asp376Asp	synonymous	Exon 9 of 15	ENSP00000288168.10
	HYDIN	ENST00000539447.5	TSL:1	n.*325T>C		non_coding_transcript_exon	Exon 7 of 19	ENSP00000463093.1

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

GnomAD2 exomes AF: 0.336 AC: 71275 AN: 212204 AF XY: 0.329

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 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

African (AFR) AF: 0.297 AC: 9720 AN: 32770

American (AMR) AF: 0.472 AC: 19856 AN: 42052

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 8142 AN: 25588

East Asian (EAS) AF: 0.457 AC: 17404 AN: 38066

South Asian (SAS) AF: 0.330 AC: 27768 AN: 84068

European-Finnish (FIN) AF: 0.232 AC: 12234 AN: 52784

Middle Eastern (MID) AF: 0.322 AC: 1820 AN: 5654

European-Non Finnish (NFE) AF: 0.258 AC: 282596 AN: 1094938

Other (OTH) AF: 0.295 AC: 17469 AN: 59288

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

African (AFR) AF: 0.294 AC: 11946 AN: 40698

American (AMR) AF: 0.389 AC: 5734 AN: 14738

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1043 AN: 3386

East Asian (EAS) AF: 0.445 AC: 2211 AN: 4968

South Asian (SAS) AF: 0.331 AC: 1542 AN: 4658

European-Finnish (FIN) AF: 0.219 AC: 2296 AN: 10490

Middle Eastern (MID) AF: 0.309 AC: 89 AN: 288

European-Non Finnish (NFE) AF: 0.266 AC: 17823 AN: 67078

Other (OTH) AF: 0.288 AC: 600 AN: 2080

Alfa AF: 0.300 Hom.: 779

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.31
DANN	Benign	0.41
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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