22-40112718-T-C

Variant names:

• chr22-40112718-T-C
• rs10483202
• ENST00000402203.5:c.-120-4337T>C

Variant summary

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

The NM_001024843.2(TNRC6B):​c.-120-4337T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0572 in 152,308 control chromosomes in the GnomAD database, including 795 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 0.057 (795 hom., cov: 32)
• Consequence: TNRC6B NM_001024843.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438
• Publications: 0 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNRC6B	NM_001024843.2	c.-120-4337T>C		intron_variant	Intron 1 of 23		NP_001020014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNRC6B	ENST00000402203.5	c.-120-4337T>C		intron_variant	Intron 1 of 23	1		ENSP00000384795.1
TNRC6B	ENST00000301923.13	c.-120-4337T>C		intron_variant	Intron 1 of 23	5		ENSP00000306759.9

Frequencies

GnomAD3 genomes AF: 0.0571 AC: 8691 AN: 152190 Hom.: 791 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0268

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00351

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00259

Gnomad OTH AF: 0.0406

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

GnomAD4 genome AF: 0.0572 AC: 8712 AN: 152308 Hom.: 795 Cov.: 32 AF XY: 0.0557 AC XY: 4150 AN XY: 74492

African (AFR) AF: 0.191 AC: 7926 AN: 41538

American (AMR) AF: 0.0267 AC: 409 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0233 AC: 81 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5190

South Asian (SAS) AF: 0.00352 AC: 17 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.00259 AC: 176 AN: 68032

Other (OTH) AF: 0.0407 AC: 86 AN: 2114

Alfa AF: 0.0302 Hom.: 135

Bravo AF: 0.0646

Asia WGS AF: 0.0240 AC: 84 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.4
DANN	Benign	0.59
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10483202; hg19: chr22-40508722;