chr12-72326012-A-C

Variant names:

• chr12-72326012-A-C
• rs17783131
• NM_013381.3:c.1188+39058A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013381.3(TRHDE):​c.1188+39058A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,036 control chromosomes in the GnomAD database, including 9,961 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 (9961 hom., cov: 32)
• Consequence: TRHDE NM_013381.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRHDE	NM_013381.3	c.1188+39058A>C		intron_variant	Intron 2 of 18	ENST00000261180.10	NP_037513.2
TRHDE	XM_017019243.3	c.1188+39058A>C		intron_variant	Intron 2 of 17		XP_016874732.3
TRHDE	XM_005268819.6	c.1188+39058A>C		intron_variant	Intron 2 of 12		XP_005268876.3
TRHDE	XM_017019244.2	c.144+39058A>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+39058A>C		intron_variant	Intron 2 of 18	1	NM_013381.3	ENSP00000261180.5
TRHDE	ENST00000547300.2	c.1188+39058A>C		intron_variant	Intron 2 of 4	3		ENSP00000447822.2
TRHDE	ENST00000548156.1	n.280-51983A>C		intron_variant	Intron 2 of 4	4
ENSG00000301751	ENST00000781341.1	n.123-1358T>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53060 AN: 151916 Hom.: 9965 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.0915

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.349 AC: 53061 AN: 152036 Hom.: 9961 Cov.: 32 AF XY: 0.346 AC XY: 25737 AN XY: 74322

African (AFR) AF: 0.239 AC: 9916 AN: 41468

American (AMR) AF: 0.283 AC: 4319 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1279 AN: 3468

East Asian (EAS) AF: 0.0917 AC: 475 AN: 5182

South Asian (SAS) AF: 0.390 AC: 1882 AN: 4822

European-Finnish (FIN) AF: 0.438 AC: 4617 AN: 10552

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29349 AN: 67972

Other (OTH) AF: 0.351 AC: 740 AN: 2108

Alfa AF: 0.367 Hom.: 1875

Bravo AF: 0.330

Asia WGS AF: 0.275 AC: 957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.75
PhyloP100		0.048
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: rs17783131; hg19: chr12-72719792;