22-40258272-T-C

Variant names:

• chr22-40258272-T-C
• rs12628051
• NM_001162501.2:c.116-3560T>C

Variant summary

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

The NM_001162501.2(TNRC6B):​c.116-3560T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 151,534 control chromosomes in the GnomAD database, including 8,301 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 0.32 (8301 hom., cov: 30)
• Consequence: TNRC6B NM_001162501.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112
• Publications: 18 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.444 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.116-3560T>C		intron	N/A	NP_001155973.1
	TNRC6B	NM_015088.3		c.116-3560T>C		intron	N/A	NP_055903.2
	TNRC6B	NM_001024843.2		c.224-3560T>C		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.116-3560T>C		intron	N/A	ENSP00000401946.2
	TNRC6B	ENST00000335727.13	TSL:1	c.116-3560T>C		intron	N/A	ENSP00000338371.8
	TNRC6B	ENST00000402203.5	TSL:1	c.224-3560T>C		intron	N/A	ENSP00000384795.1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48144 AN: 151416 Hom.: 8288 Cov.: 30

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.318 AC: 48176 AN: 151534 Hom.: 8301 Cov.: 30 AF XY: 0.326 AC XY: 24117 AN XY: 74002

African (AFR) AF: 0.198 AC: 8184 AN: 41356

American (AMR) AF: 0.422 AC: 6428 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1041 AN: 3470

East Asian (EAS) AF: 0.418 AC: 2150 AN: 5138

South Asian (SAS) AF: 0.460 AC: 2210 AN: 4800

European-Finnish (FIN) AF: 0.380 AC: 3964 AN: 10424

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23103 AN: 67822

Other (OTH) AF: 0.314 AC: 658 AN: 2094

Alfa AF: 0.336 Hom.: 28154

Bravo AF: 0.318

Asia WGS AF: 0.477 AC: 1656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.0
DANN	Benign	0.45
PhyloP100		0.11
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: rs12628051; hg19: chr22-40654276;