rs10506653

Positions:

• chr12-72338734-G-A

Variant summary

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

The NM_013381.3(TRHDE):​c.1189-39261G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 151,986 control chromosomes in the GnomAD database, including 9,868 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 0.35 (9868 hom., cov: 32)
• Consequence: TRHDE NM_013381.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRHDE	NM_013381.3	c.1189-39261G>A		intron_variant		ENST00000261180.10	NP_037513.2
TRHDE	XM_005268819.6	c.1189-39261G>A		intron_variant			XP_005268876.3
TRHDE	XM_017019243.3	c.1189-39261G>A		intron_variant			XP_016874732.3
TRHDE	XM_017019244.2	c.145-39261G>A		intron_variant			XP_016874733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRHDE	ENST00000261180.10	c.1189-39261G>A		intron_variant		1	NM_013381.3	ENSP00000261180	P1
TRHDE	ENST00000547300.2	c.1188+51780G>A		intron_variant		3		ENSP00000447822
TRHDE	ENST00000548156.1	n.280-39261G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52714 AN: 151868 Hom.: 9873 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.0890

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.347 AC: 52709 AN: 151986 Hom.: 9868 Cov.: 32 AF XY: 0.344 AC XY: 25543 AN XY: 74276

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.0892

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.348

Alfa AF: 0.409 Hom.: 6086

Bravo AF: 0.328

Asia WGS AF: 0.269 AC: 935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.68
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10506653; hg19: chr12-72732514;