16-70828290-G-C

Variant names:

• chr16-70828290-G-C
• rs879119386
• NM_001270974.2:c.14252C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001270974.2(HYDIN):​c.14252C>G​(p.Thr4751Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. T4751I) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000073 (0 hom., cov: 19)
  • Failed GnomAD Quality Control
• Consequence: HYDIN NM_001270974.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.650

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 Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09636396).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYDIN	NM_001270974.2	c.14252C>G	p.Thr4751Ser	missense_variant	Exon 82 of 86	ENST00000393567.7	NP_001257903.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYDIN	ENST00000393567.7	c.14252C>G	p.Thr4751Ser	missense_variant	Exon 82 of 86	5	NM_001270974.2	ENSP00000377197.2
HYDIN	ENST00000378856.8	n.*3008C>G		non_coding_transcript_exon_variant	Exon 17 of 22	1		ENSP00000463350.1
HYDIN	ENST00000378856.8	n.*3008C>G		3_prime_UTR_variant	Exon 17 of 22	1		ENSP00000463350.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 137326 Hom.: 0 Cov.: 19 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000155

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 8

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000728 AC: 1 AN: 137326 Hom.: 0 Cov.: 19 AF XY: 0.0000151 AC XY: 1 AN XY: 66156

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000155

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.4
DANN	Benign	0.18
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.74	D
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.4	N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.51	N
REVEL	Benign	0.078
Sift	Benign	1.0	T
Vest4		0.12
MutPred		0.42		Gain of sheet (P = 0.1208);
MVP		0.15
ClinPred		0.030	T
GERP RS		0.39
Varity_R		0.030
gMVP		0.031

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs879119386; hg19: chr16-70862193;