22-40217032-A-G

Variant names:

• chr22-40217032-A-G
• rs138022
• NM_001162501.2:c.6-28983A>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.6-28983A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 151,978 control chromosomes in the GnomAD database, including 33,582 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 0.62 (33582 hom., cov: 30)
• Consequence: TNRC6B NM_001162501.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 8 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 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.6-28983A>G		intron	N/A	NP_001155973.1	Q9UPQ9-3
	TNRC6B	NM_015088.3		c.6-28983A>G		intron	N/A	NP_055903.2	Q9UPQ9-1
	TNRC6B	NM_001024843.2		c.114-28983A>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.6-28983A>G		intron	N/A	ENSP00000401946.2	Q9UPQ9-3
	TNRC6B	ENST00000335727.13	TSL:1	c.6-28983A>G		intron	N/A	ENSP00000338371.8	Q9UPQ9-1
	TNRC6B	ENST00000402203.5	TSL:1	c.114-28983A>G		intron	N/A	ENSP00000384795.1	Q9UPQ9-2

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94110 AN: 151860 Hom.: 33575 Cov.: 30

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.690

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

GnomAD4 genome AF: 0.619 AC: 94142 AN: 151978 Hom.: 33582 Cov.: 30 AF XY: 0.630 AC XY: 46768 AN XY: 74278

African (AFR) AF: 0.241 AC: 9988 AN: 41406

American (AMR) AF: 0.784 AC: 11976 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 2499 AN: 3472

East Asian (EAS) AF: 0.987 AC: 5095 AN: 5164

South Asian (SAS) AF: 0.706 AC: 3398 AN: 4816

European-Finnish (FIN) AF: 0.780 AC: 8242 AN: 10564

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.744 AC: 50583 AN: 67968

Other (OTH) AF: 0.694 AC: 1465 AN: 2112

Alfa AF: 0.662 Hom.: 5966

Bravo AF: 0.607

Asia WGS AF: 0.809 AC: 2814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.23
DANN	Benign	0.43
PhyloP100		-1.7
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: rs138022; hg19: chr22-40613036;