rs7955732

Variant names:

• chr12-72331215-G-T
• rs7955732
• NM_013381.3:c.1188+44261G>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.1188+44261G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,068 control chromosomes in the GnomAD database, including 9,644 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 0.34 (9644 hom., cov: 32)
• Consequence: TRHDE NM_013381.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507
• Publications: 2 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]

ENSG00000301751 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.422 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.1188+44261G>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.1188+44261G>T		intron	N/A	ENSP00000261180.5	Q9UKU6
	TRHDE	ENST00000547300.2	TSL:3	c.1188+44261G>T		intron	N/A	ENSP00000447822.2	A0AA75K8V0
	TRHDE	ENST00000548156.1	TSL:4	n.280-46780G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52196 AN: 151950 Hom.: 9648 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.0885

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.343 AC: 52191 AN: 152068 Hom.: 9644 Cov.: 32 AF XY: 0.340 AC XY: 25250 AN XY: 74320

African (AFR) AF: 0.235 AC: 9744 AN: 41478

American (AMR) AF: 0.279 AC: 4265 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1276 AN: 3470

East Asian (EAS) AF: 0.0885 AC: 457 AN: 5162

South Asian (SAS) AF: 0.379 AC: 1824 AN: 4814

European-Finnish (FIN) AF: 0.425 AC: 4494 AN: 10576

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28970 AN: 67970

Other (OTH) AF: 0.344 AC: 727 AN: 2112

Alfa AF: 0.363 Hom.: 1839

Bravo AF: 0.325

Asia WGS AF: 0.260 AC: 905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.17
DANN	Benign	0.43
PhyloP100		-0.51
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: rs7955732; hg19: chr12-72724995;