22-40262052-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001162501.2(TNRC6B):c.336A>G(p.Pro112=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000252 in 1,595,106 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00026 (2 hom.)
• Consequence: TNRC6B NM_001162501.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0640

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 Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 22-40262052-A-G is Benign according to our data. Variant chr22-40262052-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2653168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.064 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000217 (33/152204) while in subpopulation SAS AF= 0.000829 (4/4826). AF 95% confidence interval is 0.000283. There are 0 homozygotes in gnomad4. There are 14 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNRC6B	NM_001162501.2	c.336A>G	p.Pro112=	synonymous_variant	4/23	ENST00000454349.7
LOC124905121	XR_007068107.1	n.304-1684T>C		intron_variant, non_coding_transcript_variant
TNRC6B	NM_015088.3	c.336A>G	p.Pro112=	synonymous_variant	4/21
TNRC6B	NM_001024843.2	c.444A>G	p.Pro148=	synonymous_variant	7/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNRC6B	ENST00000454349.7	c.336A>G	p.Pro112=	synonymous_variant	4/23	2	NM_001162501.2	P3
TNRC6B	ENST00000335727.13	c.336A>G	p.Pro112=	synonymous_variant	4/21	1
TNRC6B	ENST00000402203.5	c.444A>G	p.Pro148=	synonymous_variant	7/24	1		A2
TNRC6B	ENST00000301923.13	c.444A>G	p.Pro148=	synonymous_variant	7/24	5		A2

Frequencies

GnomAD3 genomes AF: 0.000217 AC: 33 AN: 152086 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000324

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.000387 AC: 87 AN: 224724 Hom.: 0 AF XY: 0.000468 AC XY: 57 AN XY: 121850

Gnomad AFR exome AF: 0.0000785

Gnomad AMR exome AF: 0.0000314

Gnomad ASJ exome AF: 0.00116

Gnomad EAS exome AF: 0.0000616

Gnomad SAS exome AF: 0.000862

Gnomad FIN exome AF: 0.0000494

Gnomad NFE exome AF: 0.000456

Gnomad OTH exome AF: 0.000362

GnomAD4 exome AF: 0.000256 AC: 369 AN: 1442902 Hom.: 2 Cov.: 30 AF XY: 0.000274 AC XY: 196 AN XY: 715960

Gnomad4 AFR exome AF: 0.0000302

Gnomad4 AMR exome AF: 0.0000469

Gnomad4 ASJ exome AF: 0.00109

Gnomad4 EAS exome AF: 0.0000257

Gnomad4 SAS exome AF: 0.000703

Gnomad4 FIN exome AF: 0.0000191

Gnomad4 NFE exome AF: 0.000229

Gnomad4 OTH exome AF: 0.000235

GnomAD4 genome AF: 0.000217 AC: 33 AN: 152204 Hom.: 0 Cov.: 31 AF XY: 0.000188 AC XY: 14 AN XY: 74418

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000324

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.000581 Hom.: 0

Bravo AF: 0.000242

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

TNRC6B-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 01, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

TNRC6B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	7.6
Dann	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs373838599; hg19: chr22-40658056; COSMIC: COSV57300483; COSMIC: COSV57300483;