22-40307884-C-G

Variant names:

• chr22-40307884-C-G
• rs139910
• NM_001162501.2:c.4121-628C>G

Variant summary

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

The NM_001162501.2(TNRC6B):​c.4121-628C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,888 control chromosomes in the GnomAD database, including 8,570 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 0.31 (8570 hom., cov: 31)
• Consequence: TNRC6B NM_001162501.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 3 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), G2P, Ambry Genetics, PanelApp Australia
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.509 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNRC6B	NM_001162501.2	MANE Select	c.4121-628C>G		intron	N/A	NP_001155973.1	Q9UPQ9-3
	TNRC6B	NM_015088.3		c.3791-628C>G		intron	N/A	NP_055903.2	Q9UPQ9-1
	TNRC6B	NM_001024843.2		c.1709-628C>G		intron	N/A	NP_001020014.1	Q9UPQ9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNRC6B	ENST00000454349.7	TSL:2 MANE Select	c.4121-628C>G		intron	N/A	ENSP00000401946.2	Q9UPQ9-3
	TNRC6B	ENST00000335727.13	TSL:1	c.3791-628C>G		intron	N/A	ENSP00000338371.8	Q9UPQ9-1
	TNRC6B	ENST00000446273.1	TSL:1	c.3176-628C>G		intron	N/A	ENSP00000409429.1	H0Y720

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46335 AN: 151770 Hom.: 8566 Cov.: 31

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.305 AC: 46368 AN: 151888 Hom.: 8570 Cov.: 31 AF XY: 0.296 AC XY: 22001 AN XY: 74244

African (AFR) AF: 0.515 AC: 21297 AN: 41364

American (AMR) AF: 0.181 AC: 2766 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 960 AN: 3468

East Asian (EAS) AF: 0.0130 AC: 67 AN: 5172

South Asian (SAS) AF: 0.287 AC: 1384 AN: 4814

European-Finnish (FIN) AF: 0.215 AC: 2273 AN: 10562

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16802 AN: 67948

Other (OTH) AF: 0.255 AC: 537 AN: 2106

Alfa AF: 0.118 Hom.: 142

Bravo AF: 0.308

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.28
PhyloP100		0.12
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: rs139910; hg19: chr22-40703888;