rs767570436

Variant names:

• chr12-72273151-C-A
• rs767570436
• NM_013381.3:c.508C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-72273151-C-A
• chr12-72273151-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20

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)

ACMG classification

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
TRHDE	NM_013381.3	c.508C>A	p.Pro170Thr	missense_variant	Exon 1 of 19	ENST00000261180.10	NP_037513.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRHDE	ENST00000261180.10	c.508C>A	p.Pro170Thr	missense_variant	Exon 1 of 19	1	NM_013381.3	ENSP00000261180.5

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

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

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

Other links and lift over

dbSNP: rs767570436; hg19: chr12-72666931;