12-72279043-C-T

Variant names:

• chr12-72279043-C-T
• rs4584622
• NM_013381.3:c.914+5486C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013381.3(TRHDE):​c.914+5486C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 152,090 control chromosomes in the GnomAD database, including 36,225 homozygotes. 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: 𝑓 0.69 (36225 hom., cov: 33)
• Consequence: TRHDE NM_013381.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013381.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRHDE	NM_013381.3	MANE Select	c.914+5486C>T		intron	N/A	NP_037513.2	Q9UKU6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRHDE	ENST00000261180.10	TSL:1 MANE Select	c.914+5486C>T		intron	N/A	ENSP00000261180.5	Q9UKU6
	TRHDE	ENST00000547300.2	TSL:3	c.914+5486C>T		intron	N/A	ENSP00000447822.2	A0AA75K8V0
	TRHDE	ENST00000548156.1	TSL:4	n.280-98952C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104783 AN: 151972 Hom.: 36200 Cov.: 33

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.670

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.689 AC: 104856 AN: 152090 Hom.: 36225 Cov.: 33 AF XY: 0.689 AC XY: 51227 AN XY: 74354

African (AFR) AF: 0.663 AC: 27492 AN: 41466

American (AMR) AF: 0.686 AC: 10493 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2482 AN: 3470

East Asian (EAS) AF: 0.834 AC: 4299 AN: 5154

South Asian (SAS) AF: 0.686 AC: 3302 AN: 4816

European-Finnish (FIN) AF: 0.670 AC: 7092 AN: 10582

Middle Eastern (MID) AF: 0.527 AC: 154 AN: 292

European-Non Finnish (NFE) AF: 0.698 AC: 47466 AN: 68000

Other (OTH) AF: 0.666 AC: 1407 AN: 2112

Alfa AF: 0.692 Hom.: 15258

Bravo AF: 0.688

Asia WGS AF: 0.723 AC: 2514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.4
DANN	Benign	0.88
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4584622; hg19: chr12-72672823;