22-40219272-G-T

Variant names:

• chr22-40219272-G-T
• rs739182
• NM_001162501.2:c.6-26743G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001162501.2(TNRC6B):​c.6-26743G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,072 control chromosomes in the GnomAD database, including 7,592 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (7592 hom., cov: 31)
• Consequence: TNRC6B NM_001162501.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNRC6B	NM_001162501.2	MANE Select	c.6-26743G>T		intron	N/A	NP_001155973.1
	TNRC6B	NM_015088.3		c.6-26743G>T		intron	N/A	NP_055903.2
	TNRC6B	NM_001024843.2		c.114-26743G>T		intron	N/A	NP_001020014.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNRC6B	ENST00000454349.7	TSL:2 MANE Select	c.6-26743G>T		intron	N/A	ENSP00000401946.2
	TNRC6B	ENST00000335727.13	TSL:1	c.6-26743G>T		intron	N/A	ENSP00000338371.8
	TNRC6B	ENST00000402203.5	TSL:1	c.114-26743G>T		intron	N/A	ENSP00000384795.1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44591 AN: 151954 Hom.: 7582 Cov.: 31

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.288

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.293 AC: 44620 AN: 152072 Hom.: 7592 Cov.: 31 AF XY: 0.302 AC XY: 22416 AN XY: 74340

African (AFR) AF: 0.130 AC: 5405 AN: 41502

American (AMR) AF: 0.407 AC: 6214 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1020 AN: 3472

East Asian (EAS) AF: 0.419 AC: 2162 AN: 5162

South Asian (SAS) AF: 0.449 AC: 2165 AN: 4822

European-Finnish (FIN) AF: 0.377 AC: 3983 AN: 10570

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22637 AN: 67974

Other (OTH) AF: 0.291 AC: 613 AN: 2108

Alfa AF: 0.331 Hom.: 4671

Bravo AF: 0.291

Asia WGS AF: 0.464 AC: 1612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.089
DANN	Benign	0.59
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs739182; hg19: chr22-40615276;