12-72286951-T-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_013381.3(TRHDE):c.1185T>G(p.Val395=) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.00036 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRHDE NM_013381.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.807

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 12-72286951-T-G is Benign according to our data. Variant chr12-72286951-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2643180.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.807 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRHDE	NM_013381.3	c.1185T>G	p.Val395=	synonymous_variant	2/19	ENST00000261180.10
TRHDE	XM_017019243.3	c.1185T>G	p.Val395=	synonymous_variant	2/18
TRHDE	XM_005268819.6	c.1185T>G	p.Val395=	synonymous_variant	2/13
TRHDE	XM_017019244.2	c.141T>G	p.Val47=	synonymous_variant	3/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRHDE	ENST00000261180.10	c.1185T>G	p.Val395=	synonymous_variant	2/19	1	NM_013381.3	P1
TRHDE	ENST00000547300.2	c.1185T>G	p.Val395=	synonymous_variant	2/5	3
TRHDE	ENST00000552503.1	n.349T>G		non_coding_transcript_exon_variant	2/5	4
TRHDE	ENST00000548156.1	n.280-91044T>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000360 AC: 525 AN: 1458366 Hom.: 0 Cov.: 31 AF XY: 0.000305 AC XY: 221 AN XY: 725542

Gnomad4 AFR exome AF: 0.000390

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.000105

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000429

Gnomad4 OTH exome AF: 0.000299

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

TRHDE: PM2:Supporting, BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	6.5
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-72680731;