Variant 11-78064306-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003251.4(THRSP):c.425C>T(p.Thr142Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,610,652 control chromosomes in the GnomAD database, including 178 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0086 ( 7 hom., cov: 32)

Exomes 𝑓: 0.013 ( 171 hom. )

Consequence

THRSP
NM_003251.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.68

Variant links:

Genes affected

THRSP (HGNC:11800): (thyroid hormone responsive) The protein encoded by this gene is similar to the gene product of S14, a rat gene whose expression is limited to liver and adipose tissue and is controlled by nutritional and hormonal factors. This gene has been shown to be expressed in liver and adipocytes, particularly in lipomatous modules. It is also found to be expressed in lipogenic breast cancers, which suggests a role in controlling tumor lipid metabolism. [provided by RefSeq, Jul 2008]

THRSP links:

NDUFC2-KCTD14 (HGNC:):

NDUFC2-KCTD14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039934516).

BP6

Variant 11-78064306-C-T is Benign according to our data. Variant chr11-78064306-C-T is described in ClinVar as [Benign]. Clinvar id is 771892.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
THRSP	NM_003251.4 linkuse as main transcript	c.425C>T	p.Thr142Met	missense_variant	1/2	ENST00000281030.2
NDUFC2-KCTD14	NM_001203262.2 linkuse as main transcript	c.166+15273G>A		intron_variant
NDUFC2-KCTD14	NM_001203260.2 linkuse as main transcript	c.310+8692G>A		intron_variant
NDUFC2-KCTD14	NM_001203261.2 linkuse as main transcript	c.310+8692G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THRSP	ENST00000281030.2 linkuse as main transcript	c.425C>T	p.Thr142Met	missense_variant	1/2	1	NM_003251.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00858

AC:

1301

AN:

151720

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00271

Gnomad AMI

AF:

0.00549

Gnomad AMR

AF:

0.00506

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.000389

Gnomad SAS

AF:

0.00292

Gnomad FIN

AF:

0.00720

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0148

Gnomad OTH

AF:

0.00336

GnomAD3 exomes

AF:

0.00807

AC:

2004

AN:

248190

Hom.:

AF XY:

0.00814

AC XY:

1092

AN XY:

134228

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.00325

Gnomad ASJ exome

AF:

0.000723

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00387

Gnomad FIN exome

AF:

0.00812

Gnomad NFE exome

AF:

0.0134

Gnomad OTH exome

AF:

0.0108

GnomAD4 exome

AF:

0.0126

AC:

18331

AN:

1458816

Hom.:

171

Cov.:

AF XY:

0.0121

AC XY:

8803

AN XY:

725604

show subpopulations

Gnomad4 AFR exome

AF:

0.00180

Gnomad4 AMR exome

AF:

0.00400

Gnomad4 ASJ exome

AF:

0.00112

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.00387

Gnomad4 FIN exome

AF:

0.00858

Gnomad4 NFE exome

AF:

0.0149

Gnomad4 OTH exome

AF:

0.0112

GnomAD4 genome

AF:

0.00857

AC:

1301

AN:

151836

Hom.:

Cov.:

AF XY:

0.00819

AC XY:

607

AN XY:

74150

show subpopulations

Gnomad4 AFR

AF:

0.00270

Gnomad4 AMR

AF:

0.00505

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.000390

Gnomad4 SAS

AF:

0.00292

Gnomad4 FIN

AF:

0.00720

Gnomad4 NFE

AF:

0.0148

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.0124

Hom.:

Bravo

AF:

0.00807

TwinsUK

AF:

0.0200

AC:

ALSPAC

AF:

0.0150

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0146

AC:

125

ExAC

AF:

0.00781

AC:

948

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

Cadd

Benign

Dann

Benign

0.92

DEOGEN2

Benign

0.052

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.0066

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0040

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.49

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Benign

0.28

PROVEAN

Benign

1.3

REVEL

Benign

0.037

Sift

Benign

0.19

Sift4G

Benign

0.20

Polyphen

0.32

Vest4

0.097

MVP

0.067

MPC

0.16

ClinPred

0.013

GERP RS

0.77

Varity_R

0.018

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over