14-80955693-G-C

Variant names:

• chr14-80955693-G-C
• NM_000369.5:c.13G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000369.5(TSHR):​c.13G>C​(p.Asp5His) variant causes a missense 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. 16/20 in silico tools predict 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: 33)
• Consequence: TSHR NM_000369.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05218911).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSHR	NM_000369.5	c.13G>C	p.Asp5His	missense_variant	Exon 1 of 10	ENST00000298171.7	NP_000360.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSHR	ENST00000298171.7	c.13G>C	p.Asp5His	missense_variant	Exon 1 of 10	1	NM_000369.5	ENSP00000298171.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	2.9
DANN	Benign	0.62
DEOGEN2	Benign	0.21	.;.;.;.;T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0056	N
LIST_S2	Benign	0.71	.;T;T;T;T;T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.052	T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	.;N;.;.;.;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.11	N;N;N;.;N;N
REVEL	Benign	0.087
Sift	Benign	0.37	T;T;T;.;T;T
Sift4G	Benign	0.12	T;T;T;.;T;T
Polyphen		0.0	.;B;.;.;.;.
Vest4		0.13
MutPred		0.32		Gain of catalytic residue at L7 (P = 0.0205);Gain of catalytic residue at L7 (P = 0.0205);Gain of catalytic residue at L7 (P = 0.0205);Gain of catalytic residue at L7 (P = 0.0205);Gain of catalytic residue at L7 (P = 0.0205);Gain of catalytic residue at L7 (P = 0.0205);
MVP		0.63
MPC		0.21
ClinPred		0.062	T
GERP RS		-2.7
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-81422037;