22-40261919-A-T

Variant summary

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

The NM_001162501.2(TNRC6B):c.203A>T(p.Asn68Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TNRC6B NM_001162501.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.53

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.203A>T	p.Asn68Ile	missense_variant	4/23	ENST00000454349.7
LOC124905121	XR_007068107.1	n.304-1551T>A		intron_variant, non_coding_transcript_variant
TNRC6B	NM_015088.3	c.203A>T	p.Asn68Ile	missense_variant	4/21
TNRC6B	NM_001024843.2	c.311A>T	p.Asn104Ile	missense_variant	7/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNRC6B	ENST00000454349.7	c.203A>T	p.Asn68Ile	missense_variant	4/23	2	NM_001162501.2	P3
TNRC6B	ENST00000335727.13	c.203A>T	p.Asn68Ile	missense_variant	4/21	1
TNRC6B	ENST00000402203.5	c.311A>T	p.Asn104Ile	missense_variant	7/24	1		A2
TNRC6B	ENST00000301923.13	c.311A>T	p.Asn104Ile	missense_variant	7/24	5		A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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

Invitae

Apr 03, 2022

This sequence change replaces asparagine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 68 of the TNRC6B protein (p.Asn68Ile). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals affected with TNRC6B-related conditions. This variant is not present in population databases (gnomAD no frequency). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
Cadd	Pathogenic	29
Dann	Uncertain	0.99
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	D;.;D;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.52	D;D;D;D
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	D;D;N;N
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-2.1	N;N;D;D
REVEL	Benign	0.18
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Benign	0.20	T;T;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.71
MutPred		0.22		.;.;Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);
MVP		0.29
MPC		0.71
ClinPred		0.93	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.59
gMVP		0.46

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: chr22-40657923;