16-70921012-G-C

Position:

• chr16-70921012-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001270974.2(HYDIN):​c.7364C>G​(p.Pro2455Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P2455Q) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HYDIN NM_001270974.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.45

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), HYDIN. . Gene score misZ 0.81019 (greater than the threshold 3.09). Trascript score misZ 4.6175 (greater than threshold 3.09). GenCC has associacion of gene with primary ciliary dyskinesia 5, primary ciliary dyskinesia.
• BP4: Computational evidence support a benign effect (MetaRNN=0.09032071).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HYDIN	NM_001270974.2	c.7364C>G	p.Pro2455Arg	missense_variant	46/86	ENST00000393567.7	NP_001257903.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HYDIN	ENST00000393567.7	c.7364C>G	p.Pro2455Arg	missense_variant	46/86	5	NM_001270974.2	ENSP00000377197.2
HYDIN	ENST00000309900.11	n.2036C>G		non_coding_transcript_exon_variant	12/20	1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1425638 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 709018

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	16
DANN	Benign	0.62
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.60	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.76	N
REVEL	Benign	0.17
Sift	Benign	0.41	T
Vest4		0.11
MutPred		0.23		Gain of MoRF binding (P = 0.0084);
MVP		0.30
ClinPred		0.41	T
GERP RS		5.9
Varity_R		0.034
gMVP		0.060

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1798531; hg19: chr16-70954915;