chr16-71230658-A-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_001198543.1(HYDIN):​c.28+2T>A variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,383,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HYDIN NM_001198543.1 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• 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: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000297892 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.022316685 fraction of the gene.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198543.1. 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.-120T>A		5_prime_UTR	Exon 1 of 86	NP_001257903.1	Q4G0P3-1
	HYDIN	NM_001198542.1		c.30T>A	p.Gly10Gly	synonymous	Exon 1 of 19	NP_001185471.1	Q4G0P3-8
	HYDIN	NM_017558.5		c.-120T>A		5_prime_UTR	Exon 1 of 20	NP_060028.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYDIN	ENST00000393567.7	TSL:5 MANE Select	c.-120T>A		5_prime_UTR	Exon 1 of 86	ENSP00000377197.2	Q4G0P3-1
	HYDIN	ENST00000288168.14	TSL:1	c.28+2T>A		splice_donor intron	N/A	ENSP00000288168.10	F8WD03
	HYDIN	ENST00000538248.5	TSL:2	c.30T>A	p.Gly10Gly	synonymous	Exon 1 of 19	ENSP00000444970.1	Q4G0P3-8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000732 AC: 1 AN: 136650 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000409

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1383808 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 682850

African (AFR) AF: 0.00 AC: 0 AN: 31594

American (AMR) AF: 0.0000560 AC: 2 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.00 AC: 0 AN: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33896

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078874

Other (OTH) AF: 0.00 AC: 0 AN: 57900

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	16
DANN	Benign	0.65
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.049	N
PhyloP100		0.52
GERP RS		-0.22
PromoterAI		-0.055	Neutral
Mutation Taster		=297/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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;