3-129977111-T-A

Variant names:

• chr3-129977111-T-A
• rs5662
• NM_007117.5:c.624T>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_007117.5(TRH):​c.624T>A​(p.Leu208Leu) variant causes a synonymous 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. Synonymous variant affecting the same amino acid position (i.e. L208L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: TRH NM_007117.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 11 publications found

Genes affected

TRH (HGNC:12298): (thyrotropin releasing hormone) This gene encodes a member of the thyrotropin-releasing hormone family. Cleavage of the encoded proprotein releases mature thyrotropin-releasing hormone, which is a tripeptide hypothalamic regulatory hormone. The human proprotein contains six thyrotropin-releasing hormone tripeptides. Thyrotropin-releasing hormone is involved in the regulation and release of thyroid-stimulating hormone, as well as prolactin. Deficiency of this hormone has been associated with hypothalamic hypothyroidism. [provided by RefSeq, May 2013]

LOC124906284 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=-1.03 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007117.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRH	NM_007117.5	MANE Select	c.624T>A	p.Leu208Leu	synonymous	Exon 3 of 3	NP_009048.1	P20396

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRH	ENST00000302649.4	TSL:1 MANE Select	c.624T>A	p.Leu208Leu	synonymous	Exon 3 of 3	ENSP00000303452.3	P20396
	TRH	ENST00000507066.1	TSL:5	c.612T>A	p.Leu204Leu	synonymous	Exon 3 of 3	ENSP00000426522.1	D6RFM1
	ENSG00000250643	ENST00000785099.1		n.298-5003A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 82

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.56
DANN	Benign	0.49
PhyloP100		-1.0

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: rs5662; hg19: chr3-129695954;