rs3852550

Positions:

• chr12-72612814-G-A
• chr12-72612814-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013381.3(TRHDE):​c.2322-6077G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 151,960 control chromosomes in the GnomAD database, including 14,677 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 0.41 (14677 hom., cov: 32)
• Consequence: TRHDE NM_013381.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRHDE	NM_013381.3	c.2322-6077G>A		intron_variant		ENST00000261180.10	NP_037513.2
TRHDE	XM_011538248.3	c.972-6077G>A		intron_variant			XP_011536550.1
TRHDE	XM_017019243.3	c.2322-6077G>A		intron_variant			XP_016874732.3
TRHDE	XM_017019244.2	c.1278-6077G>A		intron_variant			XP_016874733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRHDE	ENST00000261180.10	c.2322-6077G>A		intron_variant		1	NM_013381.3	ENSP00000261180	P1
TRHDE	ENST00000549138.5	n.751-6077G>A		intron_variant, non_coding_transcript_variant		5
TRHDE	ENST00000549922.1	n.218-6077G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61873 AN: 151842 Hom.: 14641 Cov.: 32

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.408 AC: 61949 AN: 151960 Hom.: 14677 Cov.: 32 AF XY: 0.408 AC XY: 30307 AN XY: 74278

Gnomad4 AFR AF: 0.651

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.576

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.397

Alfa AF: 0.345 Hom.: 1333

Bravo AF: 0.434

Asia WGS AF: 0.431 AC: 1501 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.44

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

Other links and lift over

dbSNP: rs3852550; hg19: chr12-73006594;