12-72330254-T-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013381.3(TRHDE):​c.1188+43300T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRHDE	NM_013381.3	c.1188+43300T>A		intron_variant	Intron 2 of 18	ENST00000261180.10	NP_037513.2
TRHDE	XM_017019243.3	c.1188+43300T>A		intron_variant	Intron 2 of 17		XP_016874732.3
TRHDE	XM_005268819.6	c.1188+43300T>A		intron_variant	Intron 2 of 12		XP_005268876.3
TRHDE	XM_017019244.2	c.144+43300T>A		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>A		intron_variant	Intron 2 of 18	1	NM_013381.3	ENSP00000261180.5
TRHDE	ENST00000547300.2	c.1188+43300T>A		intron_variant	Intron 2 of 4	3		ENSP00000447822.2
TRHDE	ENST00000548156.1	n.280-47741T>A		intron_variant	Intron 2 of 4	4
ENSG00000301751	ENST00000781341.1	n.122+4557A>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 7036

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	16
DANN	Benign	0.79
PhyloP100		0.58

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;