rs767570436

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013381.3(TRHDE):​c.508C>A​(p.Pro170Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,421,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. P170S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TRHDE
NM_013381.3 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.20
Variant links:
Genes affected
TRHDE (HGNC:30748): (thyrotropin releasing hormone degrading enzyme) This gene encodes a member of the peptidase M1 family. The encoded protein is an extracellular peptidase that specifically cleaves and inactivates the neuropeptide thyrotropin-releasing hormone.[provided by RefSeq, Dec 2008]
TRHDE-AS1 (HGNC:27471): (TRHDE antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1005632).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRHDENM_013381.3 linkc.508C>A p.Pro170Thr missense_variant Exon 1 of 19 ENST00000261180.10 NP_037513.2 Q9UKU6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRHDEENST00000261180.10 linkc.508C>A p.Pro170Thr missense_variant Exon 1 of 19 1 NM_013381.3 ENSP00000261180.5 Q9UKU6

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000467
AC:
1
AN:
214034
Hom.:
0
AF XY:
0.00000853
AC XY:
1
AN XY:
117240
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:
0.0000105
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000211
AC:
3
AN:
1421504
Hom.:
0
Cov.:
33
AF XY:
0.00000427
AC XY:
3
AN XY:
701980
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000275
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000830
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.064
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
21
DANN
Benign
0.94
DEOGEN2
Benign
0.074
T
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.19
FATHMM_MKL
Benign
0.62
D
LIST_S2
Benign
0.71
T
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
0.90
L
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
0.38
N
REVEL
Benign
0.070
Sift
Benign
0.055
T
Sift4G
Benign
0.12
T
Polyphen
0.0
B
Vest4
0.18
MutPred
0.29
Gain of phosphorylation at P125 (P = 0.009);
MVP
0.29
MPC
1.4
ClinPred
0.16
T
GERP RS
2.9
Varity_R
0.10
gMVP
0.61

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

LitVar

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

Other links and lift over

dbSNP: rs767570436; hg19: chr12-72666931; API