22-40195254-T-G

Variant names:

• chr22-40195254-T-G
• rs6001831
• NM_001162501.2:c.5+17114T>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.5+17114T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 152,114 control chromosomes in the GnomAD database, including 36,225 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 0.67 (36225 hom., cov: 32)
• Consequence: TNRC6B NM_001162501.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.853
• Publications: 6 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 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.5+17114T>G		intron	N/A	NP_001155973.1
	TNRC6B	NM_015088.3		c.5+17114T>G		intron	N/A	NP_055903.2
	TNRC6B	NM_001024843.2		c.113+39072T>G		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.5+17114T>G		intron	N/A	ENSP00000401946.2
	TNRC6B	ENST00000335727.13	TSL:1	c.5+17114T>G		intron	N/A	ENSP00000338371.8
	TNRC6B	ENST00000402203.5	TSL:1	c.113+39072T>G		intron	N/A	ENSP00000384795.1

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102512 AN: 151996 Hom.: 36168 Cov.: 32

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.675 AC: 102626 AN: 152114 Hom.: 36225 Cov.: 32 AF XY: 0.672 AC XY: 49982 AN XY: 74334

African (AFR) AF: 0.889 AC: 36920 AN: 41546

American (AMR) AF: 0.622 AC: 9507 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1994 AN: 3470

East Asian (EAS) AF: 0.432 AC: 2230 AN: 5166

South Asian (SAS) AF: 0.746 AC: 3600 AN: 4824

European-Finnish (FIN) AF: 0.596 AC: 6290 AN: 10560

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40095 AN: 67956

Other (OTH) AF: 0.597 AC: 1259 AN: 2108

Alfa AF: 0.656 Hom.: 4372

Bravo AF: 0.684

Asia WGS AF: 0.651 AC: 2265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.44
PhyloP100		0.85
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: rs6001831; hg19: chr22-40591258;