rs768665565

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_002775.5(HTRA1):​c.523G>A​(p.Val175Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

HTRA1
NM_002775.5 missense

Scores

13
5
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.83
Variant links:
Genes affected
HTRA1 (HGNC:9476): (HtrA serine peptidase 1) This gene encodes a member of the trypsin family of serine proteases. This protein is a secreted enzyme that is proposed to regulate the availability of insulin-like growth factors (IGFs) by cleaving IGF-binding proteins. It has also been suggested to be a regulator of cell growth. Variations in the promoter region of this gene are the cause of susceptibility to age-related macular degeneration type 7. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.786

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HTRA1NM_002775.5 linkc.523G>A p.Val175Met missense_variant 2/9 ENST00000368984.8 NP_002766.1 Q92743

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HTRA1ENST00000368984.8 linkc.523G>A p.Val175Met missense_variant 2/91 NM_002775.5 ENSP00000357980.3 Q92743
HTRA1ENST00000648167.1 linkc.205G>A p.Val69Met missense_variant 2/9 ENSP00000498033.1 A0A3B3IU24

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251496
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135922
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461862
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727234
show subpopulations
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:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAthena DiagnosticsOct 01, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.34
D
BayesDel_noAF
Pathogenic
0.25
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.45
.;T
Eigen
Pathogenic
0.94
Eigen_PC
Pathogenic
0.88
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
D;D
M_CAP
Uncertain
0.094
D
MetaRNN
Pathogenic
0.79
D;D
MetaSVM
Pathogenic
0.89
D
MutationAssessor
Uncertain
2.9
.;M
PrimateAI
Pathogenic
0.93
D
PROVEAN
Uncertain
-2.5
.;D
REVEL
Pathogenic
0.75
Sift
Pathogenic
0.0
.;D
Sift4G
Uncertain
0.0020
.;D
Polyphen
1.0
.;D
Vest4
0.88
MutPred
0.40
.;Gain of ubiquitination at K178 (P = 0.1575);
MVP
0.96
MPC
1.4
ClinPred
0.99
D
GERP RS
5.4
Varity_R
0.84
gMVP
0.87

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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: rs768665565; hg19: chr10-124248468; API