16-71129790-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001270974.2(HYDIN):​c.1077T>A​(p.Asp359Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,438,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: not found (cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HYDIN NM_001270974.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70

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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.020637482).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYDIN	NM_001270974.2	c.1077T>A	p.Asp359Glu	missense_variant	Exon 9 of 86	ENST00000393567.7	NP_001257903.1
HYDIN	NM_017558.5	c.1077T>A	p.Asp359Glu	missense_variant	Exon 9 of 20		NP_060028.2
HYDIN	NM_001198542.1	c.1158T>A	p.Asp386Glu	missense_variant	Exon 9 of 19		NP_001185471.1
HYDIN	NM_001198543.1	c.1128T>A	p.Asp376Glu	missense_variant	Exon 9 of 19		NP_001185472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYDIN	ENST00000393567.7	c.1077T>A	p.Asp359Glu	missense_variant	Exon 9 of 86	5	NM_001270974.2	ENSP00000377197.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1438316 Hom.: 0 Cov.: 33 AF XY: 0.00000140 AC XY: 1 AN XY: 715568

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: 0.00000182

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.14
DANN	Benign	0.19
DEOGEN2	Benign	0.025	T;.;.;.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.020	N
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.021	T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.82	L;L;.;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.21	N;N;N;N;N
REVEL	Benign	0.031
Sift	Benign	1.0	T;T;T;T;T
Sift4G	Benign	0.53	.;T;T;T;T
Polyphen		0.0060, 0.0020	.;B;.;.;B
Vest4		0.067
MutPred		0.31		.;.;.;Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);
MVP		0.11
ClinPred		0.033	T
GERP RS		-5.9
Varity_R		0.044
gMVP		0.038

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-71163693;