chr22-40156121-C-A

Position:

• chr22-40156121-C-A

Variant summary

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

The NM_001024843.2(TNRC6B):​c.52C>A​(p.Gln18Lys) 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNRC6B NM_001024843.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.81

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=0.1690019).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNRC6B	NM_001024843.2	c.52C>A	p.Gln18Lys	missense_variant	4/24		NP_001020014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNRC6B	ENST00000402203.5	c.52C>A	p.Gln18Lys	missense_variant	4/24	1		ENSP00000384795.1
TNRC6B	ENST00000301923.13	c.52C>A	p.Gln18Lys	missense_variant	4/24	5		ENSP00000306759.9
TNRC6B	ENST00000441751.5	c.52C>A	p.Gln18Lys	missense_variant	4/4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1426950 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 706022

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

Mar 19, 2024

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Reported using an alternate transcript of the gene -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	24
DANN	Uncertain	0.99
Eigen	Benign	0.093
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.74	T;T;.
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.98	N;N
PROVEAN	Uncertain	-3.4	D;N;N
REVEL	Benign	0.066
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.37	T;T;T
Polyphen		0.012	.;B;B
Vest4		0.26, 0.28
MutPred		0.27		Gain of ubiquitination at Q18 (P = 0.0022);Gain of ubiquitination at Q18 (P = 0.0022);Gain of ubiquitination at Q18 (P = 0.0022);
MVP		0.29
ClinPred		0.78	D
GERP RS		5.7

Splicing

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: chr22-40552125;