22-40156173-A-C

Position:

• chr22-40156173-A-C

Variant summary

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

The NM_001024843.2(TNRC6B):​c.104A>C​(p.Glu35Ala) 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: 5.72

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=0.25716656).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNRC6B	NM_001024843.2	c.104A>C	p.Glu35Ala	missense_variant	4/24		NP_001020014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNRC6B	ENST00000402203.5	c.104A>C	p.Glu35Ala	missense_variant	4/24	1		ENSP00000384795.1
TNRC6B	ENST00000301923.13	c.104A>C	p.Glu35Ala	missense_variant	4/24	5		ENSP00000306759.9
TNRC6B	ENST00000441751.5	c.104A>C	p.Glu35Ala	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: 1421564 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 702990

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

See cases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

New York Genome Center

Feb 05, 2021

The c.104A>C, p.Glu35Ala missense variant identified in TNRC6B has not been reported in the literature. This variant is absent in the gnomAD v3 database, indicating this is a rare allele. In silico analysis predicts conflicting interpretations of pathogenicity [PMID:27268795]. Based on the available evidence, the missense variant c.104A>C, p.Glu35Ala in the TNRC6B gene is classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	0.0033	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	27
DANN	Uncertain	1.0
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.73	T;T;.
M_CAP	Benign	0.081	D
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-0.78	T
PROVEAN	Pathogenic	-6.0	D;N;N
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;T;T
Polyphen		0.97	.;D;D
Vest4		0.41, 0.41
MutPred		0.067		Loss of solvent accessibility (P = 0.0769);Loss of solvent accessibility (P = 0.0769);Loss of solvent accessibility (P = 0.0769);
MVP		0.38
ClinPred		0.98	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1601847316; hg19: chr22-40552177; COSMIC: COSV57290264;