dbSNP rs1442442750: TNRC6B:p.Thr51Lys (chr22-40261868-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001162501.2(TNRC6B):c.152C>A(p.Thr51Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,430,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TNRC6B
NM_001162501.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.46

Variant links:

Genes affected

TNRC6B (HGNC:29190): (trinucleotide repeat containing adaptor 6B) Enables RNA binding activity. Involved in regulation of gene expression. Predicted to be located in cytosol. Predicted to be active in P-body and nucleoplasm. Implicated in subserous uterine fibroid and uterine fibroid. [provided by Alliance of Genome Resources, Apr 2022]

TNRC6B links:

LOC124905121 (HGNC:):

LOC124905121 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13276306).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNRC6B	NM_001162501.2 link	c.152C>A	p.Thr51Lys	missense_variant	Exon 4 of 23	ENST00000454349.7	NP_001155973.1	Q9UPQ9-3
TNRC6B	NM_015088.3 link	c.152C>A	p.Thr51Lys	missense_variant	Exon 4 of 21		NP_055903.2	Q9UPQ9-1
TNRC6B	NM_001024843.2 link	c.260C>A	p.Thr87Lys	missense_variant	Exon 7 of 24		NP_001020014.1	Q9UPQ9-2A0A024R1N5
LOC124905121	XR_007068107.1 link	n.304-1500G>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TNRC6B	ENST00000454349.7 link	c.152C>A	p.Thr51Lys	missense_variant	Exon 4 of 23	2	NM_001162501.2	ENSP00000401946.2	Q9UPQ9-3
TNRC6B	ENST00000335727.13 link	c.152C>A	p.Thr51Lys	missense_variant	Exon 4 of 21	1		ENSP00000338371.8	Q9UPQ9-1
TNRC6B	ENST00000402203.5 link	c.260C>A	p.Thr87Lys	missense_variant	Exon 7 of 24	1		ENSP00000384795.1	Q9UPQ9-2
TNRC6B	ENST00000301923.13 link	c.260C>A	p.Thr87Lys	missense_variant	Exon 7 of 24	5		ENSP00000306759.9	Q9UPQ9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000410

AC:

AN:

243702

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133068

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000919

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000210

AC:

AN:

1430080

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

706296

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000276

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.015

.;.;T;.

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.93

D;.;D;D

M_CAP

Benign

0.0044

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.76

.;.;N;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.67

N;N;N;N

REVEL

Benign

0.037

Sift

Benign

0.10

T;T;T;T

Sift4G

Benign

0.81

T;T;T;T

Polyphen

0.15

B;B;B;B

Vest4

0.45

MutPred

0.31

.;.;Gain of ubiquitination at T51 (P = 0.0018);Gain of ubiquitination at T51 (P = 0.0018);

MVP

0.10

MPC

0.24

ClinPred

0.40

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.077

gMVP

0.10

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over