22-40261976-T-C

Variant summary

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

The NM_001162501.2(TNRC6B):c.260T>C(p.Met87Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNRC6B NM_001162501.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.82

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]

LOC124905121 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNRC6B	NM_001162501.2	c.260T>C	p.Met87Thr	missense_variant	4/23	ENST00000454349.7
LOC124905121	XR_007068107.1	n.304-1608A>G		intron_variant, non_coding_transcript_variant
TNRC6B	NM_015088.3	c.260T>C	p.Met87Thr	missense_variant	4/21
TNRC6B	NM_001024843.2	c.368T>C	p.Met123Thr	missense_variant	7/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNRC6B	ENST00000454349.7	c.260T>C	p.Met87Thr	missense_variant	4/23	2	NM_001162501.2	P3
TNRC6B	ENST00000335727.13	c.260T>C	p.Met87Thr	missense_variant	4/21	1
TNRC6B	ENST00000402203.5	c.368T>C	p.Met123Thr	missense_variant	7/24	1		A2
TNRC6B	ENST00000301923.13	c.368T>C	p.Met123Thr	missense_variant	7/24	5		A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460116 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726342

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Sep 22, 2022

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
Cadd	Pathogenic	27
Dann	Uncertain	0.99
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D;.;D;D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.58	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.84	D;D;D;D
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.66	N;N;N;N
REVEL	Benign	0.19
Sift	Uncertain	0.021	D;D;D;D
Sift4G	Benign	0.43	T;T;D;T
Polyphen		0.96	D;D;D;D
Vest4		0.79
MutPred		0.16		.;.;Gain of phosphorylation at M87 (P = 0.002);Gain of phosphorylation at M87 (P = 0.002);
MVP		0.35
MPC		0.65
ClinPred		0.72	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.38
gMVP		0.34

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: chr22-40657980;