22-40246097-C-G

Position:

• chr22-40246097-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001162501.2(TNRC6B):​c.88C>G​(p.Gln30Glu) variant causes a missense change. 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 Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TNRC6B NM_001162501.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 5.14

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 (HGNC:):

ACMG classification

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=0.09831008).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNRC6B	NM_001162501.2	c.88C>G	p.Gln30Glu	missense_variant	2/23	ENST00000454349.7	NP_001155973.1
TNRC6B	NM_015088.3	c.88C>G	p.Gln30Glu	missense_variant	2/21		NP_055903.2
TNRC6B	NM_001024843.2	c.196C>G	p.Gln66Glu	missense_variant	5/24		NP_001020014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNRC6B	ENST00000454349.7	c.88C>G	p.Gln30Glu	missense_variant	2/23	2	NM_001162501.2	ENSP00000401946.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

TNRC6B-related disorder Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 09, 2024

The TNRC6B c.88C>G variant is predicted to result in the amino acid substitution p.Gln30Glu. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.016	.;.;T;.
Eigen	Benign	-0.057
Eigen_PC	Benign	0.031
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D;.;T;D
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.098	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	.;.;M;M
MutationTaster	Benign	0.93	D;D;N;N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.50	N;N;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.014	D;D;D;D
Sift4G	Benign	0.51	T;T;D;T
Polyphen		0.10	B;B;B;B
Vest4		0.24
MutPred		0.090		.;.;Loss of MoRF binding (P = 0.0576);Loss of MoRF binding (P = 0.0576);
MVP		0.15
MPC		0.16
ClinPred		0.71	D
GERP RS		3.4
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.20
gMVP		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-40642101;