12-72612127-A-T

Variant summary

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

The NM_013381.3(TRHDE):​c.2322-6764A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 31)

Consequence

TRHDE
NM_013381.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00700
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]

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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 (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TRHDENM_013381.3 linkuse as main transcriptc.2322-6764A>T intron_variant ENST00000261180.10 NP_037513.2
TRHDEXM_011538248.3 linkuse as main transcriptc.972-6764A>T intron_variant XP_011536550.1
TRHDEXM_017019243.3 linkuse as main transcriptc.2322-6764A>T intron_variant XP_016874732.3
TRHDEXM_017019244.2 linkuse as main transcriptc.1278-6764A>T intron_variant XP_016874733.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TRHDEENST00000261180.10 linkuse as main transcriptc.2322-6764A>T intron_variant 1 NM_013381.3 ENSP00000261180 P1
TRHDEENST00000549138.5 linkuse as main transcriptn.751-6764A>T intron_variant, non_coding_transcript_variant 5
TRHDEENST00000549922.1 linkuse as main transcriptn.218-6764A>T intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
3.9
DANN
Benign
0.44

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: rs3852549; hg19: chr12-73005907; API