22-40261951-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001162501.2(TNRC6B):c.235C>A(p.Gln79Lys) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 31)
• Consequence: TNRC6B NM_001162501.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.38

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28818643).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNRC6B	NM_001162501.2	c.235C>A	p.Gln79Lys	missense_variant	4/23	ENST00000454349.7
LOC124905121	XR_007068107.1	n.304-1583G>T		intron_variant, non_coding_transcript_variant
TNRC6B	NM_015088.3	c.235C>A	p.Gln79Lys	missense_variant	4/21
TNRC6B	NM_001024843.2	c.343C>A	p.Gln115Lys	missense_variant	7/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNRC6B	ENST00000454349.7	c.235C>A	p.Gln79Lys	missense_variant	4/23	2	NM_001162501.2	P3
TNRC6B	ENST00000335727.13	c.235C>A	p.Gln79Lys	missense_variant	4/21	1
TNRC6B	ENST00000402203.5	c.343C>A	p.Gln115Lys	missense_variant	7/24	1		A2
TNRC6B	ENST00000301923.13	c.343C>A	p.Gln115Lys	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

GeneDx

Jan 19, 2023

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	0.73
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.29
Cadd	Pathogenic	28
Dann	Uncertain	0.99
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;.;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.29	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;N;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.49	N;N;N;N
REVEL	Benign	0.15
Sift	Uncertain	0.0080	D;D;D;D
Sift4G	Benign	0.42	T;T;T;T
Polyphen		0.40	B;B;P;P
Vest4		0.77
MutPred		0.15		.;.;Gain of methylation at Q79 (P = 0.0127);Gain of methylation at Q79 (P = 0.0127);
MVP		0.27
MPC		0.70
ClinPred		0.78	D
GERP RS		5.9
Varity_R		0.46
gMVP		0.43

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: chr22-40657955;