rs2899334

Variant names:

• chr22-40155846-T-C
• rs2899334
• ENST00000402203.5:c.46-269T>C

Variant summary

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

The ENST00000402203.5(TNRC6B):​c.46-269T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 152,140 control chromosomes in the GnomAD database, including 36,798 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 0.68 (36798 hom., cov: 33)
• Consequence: TNRC6B ENST00000402203.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNRC6B	NM_001024843.2	c.46-269T>C		intron_variant	Intron 3 of 23		NP_001020014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNRC6B	ENST00000402203.5	c.46-269T>C		intron_variant	Intron 3 of 23	1		ENSP00000384795.1
TNRC6B	ENST00000301923.13	c.46-269T>C		intron_variant	Intron 3 of 23	5		ENSP00000306759.9

Frequencies

GnomAD3 genomes AF: 0.678 AC: 103113 AN: 152022 Hom.: 36733 Cov.: 33

Gnomad AFR AF: 0.904

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.679 AC: 103235 AN: 152140 Hom.: 36798 Cov.: 33 AF XY: 0.676 AC XY: 50291 AN XY: 74364

African (AFR) AF: 0.904 AC: 37550 AN: 41556

American (AMR) AF: 0.623 AC: 9526 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1993 AN: 3470

East Asian (EAS) AF: 0.429 AC: 2210 AN: 5156

South Asian (SAS) AF: 0.747 AC: 3594 AN: 4812

European-Finnish (FIN) AF: 0.596 AC: 6300 AN: 10564

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.589 AC: 40076 AN: 67986

Other (OTH) AF: 0.605 AC: 1276 AN: 2110

Alfa AF: 0.666 Hom.: 5193

Bravo AF: 0.688

Asia WGS AF: 0.656 AC: 2281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.4
DANN	Benign	0.53
PhyloP100		0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2899334; hg19: chr22-40551850;