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GeneBe

12-72273276-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_013381.3(TRHDE):c.633G>A(p.Glu211=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0044 in 1,614,098 control chromosomes in the GnomAD database, including 262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.024 ( 144 hom., cov: 32)
Exomes 𝑓: 0.0024 ( 118 hom. )

Consequence

TRHDE
NM_013381.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.29
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 Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-72273276-G-A is Benign according to our data. Variant chr12-72273276-G-A is described in ClinVar as [Benign]. Clinvar id is 784247.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.29 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0785 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRHDENM_013381.3 linkuse as main transcriptc.633G>A p.Glu211= synonymous_variant 1/19 ENST00000261180.10
TRHDE-AS1NR_026837.1 linkuse as main transcriptn.234C>T non_coding_transcript_exon_variant 1/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRHDEENST00000261180.10 linkuse as main transcriptc.633G>A p.Glu211= synonymous_variant 1/191 NM_013381.3 P1
TRHDE-AS1ENST00000663912.1 linkuse as main transcriptn.134+3545C>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0235
AC:
3573
AN:
152188
Hom.:
142
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0808
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0113
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000382
Gnomad OTH
AF:
0.0124
GnomAD3 exomes
AF:
0.00615
AC:
1541
AN:
250770
Hom.:
59
AF XY:
0.00449
AC XY:
609
AN XY:
135770
show subpopulations
Gnomad AFR exome
AF:
0.0833
Gnomad AMR exome
AF:
0.00428
Gnomad ASJ exome
AF:
0.000398
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000212
Gnomad OTH exome
AF:
0.00179
GnomAD4 exome
AF:
0.00241
AC:
3520
AN:
1461792
Hom.:
118
Cov.:
33
AF XY:
0.00208
AC XY:
1510
AN XY:
727196
show subpopulations
Gnomad4 AFR exome
AF:
0.0834
Gnomad4 AMR exome
AF:
0.00463
Gnomad4 ASJ exome
AF:
0.000497
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000197
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000128
Gnomad4 OTH exome
AF:
0.00530
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0235
AC:
3584
AN:
152306
Hom.:
144
Cov.:
32
AF XY:
0.0225
AC XY:
1678
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.0808
Gnomad4 AMR
AF:
0.0112
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000382
Gnomad4 OTH
AF:
0.0123
Alfa
AF:
0.0116
Hom.:
40
Bravo
AF:
0.0272
Asia WGS
AF:
0.00491
AC:
17
AN:
3478
EpiCase
AF:
0.000327
EpiControl
AF:
0.000178

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeNov 15, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.36
Cadd
Benign
14
Dann
Benign
0.97

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: rs9651989; hg19: chr12-72667056; API