22-40261889-G-A

Position:

• chr22-40261889-G-A

Variant summary

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

The NM_001162501.2(TNRC6B):​c.173G>A​(p.Ser58Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNRC6B NM_001162501.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.56

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07246348).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNRC6B	NM_001162501.2	c.173G>A	p.Ser58Asn	missense_variant	4/23	ENST00000454349.7	NP_001155973.1
TNRC6B	NM_015088.3	c.173G>A	p.Ser58Asn	missense_variant	4/21		NP_055903.2
TNRC6B	NM_001024843.2	c.281G>A	p.Ser94Asn	missense_variant	7/24		NP_001020014.1
LOC124905121	XR_007068107.1	n.304-1521C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNRC6B	ENST00000454349.7	c.173G>A	p.Ser58Asn	missense_variant	4/23	2	NM_001162501.2	ENSP00000401946.2
TNRC6B	ENST00000335727.13	c.173G>A	p.Ser58Asn	missense_variant	4/21	1		ENSP00000338371.8
TNRC6B	ENST00000402203.5	c.281G>A	p.Ser94Asn	missense_variant	7/24	1		ENSP00000384795.1
TNRC6B	ENST00000301923.13	c.281G>A	p.Ser94Asn	missense_variant	7/24	5		ENSP00000306759.9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1443188 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 715186

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.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 30, 2024

The c.173G>A (p.S58N) alteration is located in exon 4 (coding exon 4) of the TNRC6B gene. This alteration results from a G to A substitution at nucleotide position 173, causing the serine (S) at amino acid position 58 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Uncertain	23
DANN	Benign	0.92
DEOGEN2	Benign	0.0098	.;.;T;.
Eigen	Benign	0.025
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.85	T;.;T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.072	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	.;.;L;L
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.47	N;N;N;N
REVEL	Benign	0.082
Sift	Benign	0.057	T;T;T;D
Sift4G	Benign	0.35	T;T;T;T
Polyphen		0.0	B;B;B;B
Vest4		0.26
MutPred		0.075		.;.;Loss of phosphorylation at S58 (P = 0.0105);Loss of phosphorylation at S58 (P = 0.0105);
MVP		0.12
MPC		0.14
ClinPred		0.53	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.091

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

LitVar

Other links and lift over

dbSNP: rs1314560053; hg19: chr22-40657893;