Genetic Variant TSHR:c.170+26188T>C (chr14-80982038-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000369.5(TSHR):c.170+26188T>C 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: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TSHR
NM_000369.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.56

Publications

9 publications found

Variant links:

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]

TSHR links:

GPRASP3P1 (HGNC:51373): (GPRASP3 pseudogene 1)

GPRASP3P1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.07).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TSHR	NM_000369.5 link	c.170+26188T>C	intron_variant	Intron 1 of 9	ENST00000298171.7	NP_000360.2	P16473A0A0A0MTJ0
GPRASP3P1		n.80982038T>C	intragenic_variant
TSHR	NM_001142626.3 link	c.170+26188T>C	intron_variant	Intron 1 of 8		NP_001136098.1	P16473-3
TSHR	NM_001018036.3 link	c.170+26188T>C	intron_variant	Intron 1 of 8		NP_001018046.1	P16473-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSHR	ENST00000298171.7 link	c.170+26188T>C		intron_variant	Intron 1 of 9	1	NM_000369.5	ENSP00000298171.2		A0A0A0MTJ0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

264598

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

143338

African (AFR)

AF:

0.00

AC:

AN:

7710

American (AMR)

AF:

0.00

AC:

AN:

19398

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6428

East Asian (EAS)

AF:

0.00

AC:

AN:

14612

South Asian (SAS)

AF:

0.00

AC:

AN:

26252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28004

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1500

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

147086

Other (OTH)

AF:

0.00

AC:

AN:

13608

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

2.4

(source)

DANN

Benign

0.32

PhyloP100

-1.6

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over