12-72319592-A-G

Variant names:

• chr12-72319592-A-G
• rs7957269
• NM_013381.3:c.1188+32638A>G

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+32638A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 152,016 control chromosomes in the GnomAD database, including 29,560 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 0.61 (29560 hom., cov: 32)
• Consequence: TRHDE NM_013381.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.555
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.691 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRHDE	NM_013381.3	MANE Select	c.1188+32638A>G		intron	N/A	NP_037513.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRHDE	ENST00000261180.10	TSL:1 MANE Select	c.1188+32638A>G		intron	N/A	ENSP00000261180.5
	TRHDE	ENST00000547300.2	TSL:3	c.1188+32638A>G		intron	N/A	ENSP00000447822.2
	TRHDE	ENST00000548156.1	TSL:4	n.280-58403A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93376 AN: 151898 Hom.: 29550 Cov.: 32

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.615 AC: 93414 AN: 152016 Hom.: 29560 Cov.: 32 AF XY: 0.617 AC XY: 45859 AN XY: 74294

African (AFR) AF: 0.475 AC: 19693 AN: 41456

American (AMR) AF: 0.581 AC: 8872 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1986 AN: 3464

East Asian (EAS) AF: 0.445 AC: 2291 AN: 5154

South Asian (SAS) AF: 0.694 AC: 3347 AN: 4820

European-Finnish (FIN) AF: 0.745 AC: 7878 AN: 10570

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47307 AN: 67964

Other (OTH) AF: 0.585 AC: 1236 AN: 2112

Alfa AF: 0.645 Hom.: 4509

Bravo AF: 0.590

Asia WGS AF: 0.569 AC: 1980 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.43
DANN	Benign	0.73
PhyloP100		-0.56
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: rs7957269; hg19: chr12-72713372;