chr16-70807800-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001270974.2(HYDIN):ā€‹c.15146T>Gā€‹(p.Met5049Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,316 control chromosomes in the GnomAD database, with no homozygous occurrence. 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.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)

Consequence

HYDIN
NM_001270974.2 missense

Scores

17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.09
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06253788).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HYDINNM_001270974.2 linkc.15146T>G p.Met5049Arg missense_variant Exon 86 of 86 ENST00000393567.7 NP_001257903.1 Q4G0P3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HYDINENST00000393567.7 linkc.15146T>G p.Met5049Arg missense_variant Exon 86 of 86 5 NM_001270974.2 ENSP00000377197.2 Q4G0P3-1
HYDINENST00000378856.8 linkn.*4026T>G non_coding_transcript_exon_variant Exon 22 of 22 1 ENSP00000463350.1 J3QL30
HYDINENST00000378856.8 linkn.*4026T>G 3_prime_UTR_variant Exon 22 of 22 1 ENSP00000463350.1 J3QL30

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152198
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249570
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135400
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000556
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152316
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000826
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
17
DANN
Benign
0.64
DEOGEN2
Benign
0.031
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.14
N
M_CAP
Benign
0.0054
T
MetaRNN
Benign
0.063
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.69
N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.080
N
REVEL
Benign
0.081
Sift
Benign
0.044
D
Vest4
0.25
MutPred
0.61
Gain of catalytic residue at M5049 (P = 0.0301);
MVP
0.014
ClinPred
0.088
T
GERP RS
3.1
Varity_R
0.33
gMVP
0.33

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs116730273; hg19: chr16-70841703; API