NM_000369.5:c.60C>T

Variant names:

• chr14-80955740-C-T
• rs2139669504
• NM_000369.5:c.60C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_000369.5(TSHR):​c.60C>T​(p.Gly20Gly) 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TSHR NM_000369.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.494
• Publications: 0 publications found

Genes affected

TSHR (HGNC:12373): (thyroid stimulating hormone receptor) The protein encoded by this gene is a membrane protein and a major controller of thyroid cell metabolism. The encoded protein is a receptor for thyrothropin and thyrostimulin, and its activity is mediated by adenylate cyclase. Defects in this gene are a cause of several types of hyperthyroidism. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

CEP128 (HGNC:20359): (centrosomal protein 128) Involved in protein localization. Located in centriole and spindle pole. Part of centriolar subdistal appendage. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 14-80955740-C-T is Benign according to our data. Variant chr14-80955740-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2866199.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.494 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000369.5. 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
	TSHR	NM_000369.5	MANE Select	c.60C>T	p.Gly20Gly	synonymous	Exon 1 of 10	NP_000360.2	P16473-1
	TSHR	NM_001142626.3		c.60C>T	p.Gly20Gly	synonymous	Exon 1 of 9	NP_001136098.1	P16473-3
	TSHR	NM_001018036.3		c.60C>T	p.Gly20Gly	synonymous	Exon 1 of 9	NP_001018046.1	P16473-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSHR	ENST00000298171.7	TSL:1 MANE Select	c.60C>T	p.Gly20Gly	synonymous	Exon 1 of 10	ENSP00000298171.2	P16473-1
	TSHR	ENST00000554435.1	TSL:1	c.60C>T	p.Gly20Gly	synonymous	Exon 1 of 9	ENSP00000450549.1	P16473-3
	TSHR	ENST00000342443.10	TSL:1	c.60C>T	p.Gly20Gly	synonymous	Exon 1 of 9	ENSP00000340113.6	P16473-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.0
DANN	Benign	0.88
PhyloP100		-0.49
PromoterAI		-0.025	Neutral

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: rs2139669504; hg19: chr14-81422084; COSMIC: COSV53319471; COSMIC: COSV53319471;