chr22-40246097-C-G

Variant names:

• chr22-40246097-C-G
• NM_001162501.2:c.88C>G

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• global developmental delay with speech and behavioral abnormalities

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09831008).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001162501.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNRC6B	NM_001162501.2	MANE Select	c.88C>G	p.Gln30Glu	missense	Exon 2 of 23	NP_001155973.1	Q9UPQ9-3
	TNRC6B	NM_015088.3		c.88C>G	p.Gln30Glu	missense	Exon 2 of 21	NP_055903.2	Q9UPQ9-1
	TNRC6B	NM_001024843.2		c.196C>G	p.Gln66Glu	missense	Exon 5 of 24	NP_001020014.1	Q9UPQ9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNRC6B	ENST00000454349.7	TSL:2 MANE Select	c.88C>G	p.Gln30Glu	missense	Exon 2 of 23	ENSP00000401946.2	Q9UPQ9-3
	TNRC6B	ENST00000335727.13	TSL:1	c.88C>G	p.Gln30Glu	missense	Exon 2 of 21	ENSP00000338371.8	Q9UPQ9-1
	TNRC6B	ENST00000402203.5	TSL:1	c.196C>G	p.Gln66Glu	missense	Exon 5 of 24	ENSP00000384795.1	Q9UPQ9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	TNRC6B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.1
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.12
Sift	Uncertain	0.014	D
Sift4G	Benign	0.51	T
Polyphen		0.10	B
Vest4		0.24
MutPred		0.090		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
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

hg19: chr22-40642101;