12-72330254-T-C

Position:

• chr12-72330254-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_013381.3(TRHDE):​c.1188+43300T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 151,188 control chromosomes in the GnomAD database, including 2,003 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 0.15 (2003 hom., cov: 31)
• Consequence: TRHDE NM_013381.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.576

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRHDE	NM_013381.3	c.1188+43300T>C		intron_variant		ENST00000261180.10	NP_037513.2
TRHDE	XM_005268819.6	c.1188+43300T>C		intron_variant			XP_005268876.3
TRHDE	XM_017019243.3	c.1188+43300T>C		intron_variant			XP_016874732.3
TRHDE	XM_017019244.2	c.144+43300T>C		intron_variant			XP_016874733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRHDE	ENST00000261180.10	c.1188+43300T>C		intron_variant		1	NM_013381.3	ENSP00000261180	P1
TRHDE	ENST00000547300.2	c.1188+43300T>C		intron_variant		3		ENSP00000447822
TRHDE	ENST00000548156.1	n.280-47741T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22503 AN: 151070 Hom.: 2003 Cov.: 31

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.0562

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.149 AC: 22511 AN: 151188 Hom.: 2003 Cov.: 31 AF XY: 0.151 AC XY: 11152 AN XY: 73806

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.157

Alfa AF: 0.125 Hom.: 3261

Bravo AF: 0.156

Asia WGS AF: 0.261 AC: 907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	17
DANN	Benign	0.76

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: rs12831974; hg19: chr12-72724034;