12-72330254-T-C

Variant names:

• chr12-72330254-T-C
• rs12831974
• NM_013381.3:c.1188+43300T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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 -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 rank	MANE	Protein	UniProt
TRHDE	NM_013381.3	c.1188+43300T>C		intron_variant	Intron 2 of 18	ENST00000261180.10	NP_037513.2
TRHDE	XM_017019243.3	c.1188+43300T>C		intron_variant	Intron 2 of 17		XP_016874732.3
TRHDE	XM_005268819.6	c.1188+43300T>C		intron_variant	Intron 2 of 12		XP_005268876.3
TRHDE	XM_017019244.2	c.144+43300T>C		intron_variant	Intron 3 of 19		XP_016874733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRHDE	ENST00000261180.10	c.1188+43300T>C		intron_variant	Intron 2 of 18	1	NM_013381.3	ENSP00000261180.5
TRHDE	ENST00000547300.2	c.1188+43300T>C		intron_variant	Intron 2 of 4	3		ENSP00000447822.2
TRHDE	ENST00000548156.1	n.280-47741T>C		intron_variant	Intron 2 of 4	4
ENSG00000301751	ENST00000781341.1	n.122+4557A>G		intron_variant	Intron 1 of 1

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

African (AFR) AF: 0.173 AC: 7120 AN: 41102

American (AMR) AF: 0.161 AC: 2445 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 524 AN: 3466

East Asian (EAS) AF: 0.478 AC: 2442 AN: 5114

South Asian (SAS) AF: 0.124 AC: 593 AN: 4786

European-Finnish (FIN) AF: 0.121 AC: 1251 AN: 10346

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.114 AC: 7709 AN: 67890

Other (OTH) AF: 0.157 AC: 330 AN: 2098

Alfa AF: 0.130 Hom.: 7036

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
PhyloP100		0.58
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: rs12831974; hg19: chr12-72724034;