chr22-40333610-A-G

Variant names:

• chr22-40333610-A-G
• rs470113
• NM_001162501.2:c.*10369A>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.*10369A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,526 control chromosomes in the GnomAD database, including 3,557 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 0.20 (3545 hom., cov: 31)
  • Exomes 𝑓: 0.21 (12 hom.)
• Consequence: TNRC6B NM_001162501.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350
• Publications: 25 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNRC6B	NM_001162501.2	c.*10369A>G		3_prime_UTR_variant	Exon 23 of 23	ENST00000454349.7	NP_001155973.1
TNRC6B	NM_015088.3	c.*10369A>G		3_prime_UTR_variant	Exon 21 of 21		NP_055903.2
TNRC6B	NM_001024843.2	c.*10369A>G		3_prime_UTR_variant	Exon 24 of 24		NP_001020014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNRC6B	ENST00000454349.7	c.*10369A>G		3_prime_UTR_variant	Exon 23 of 23	2	NM_001162501.2	ENSP00000401946.2
TNRC6B	ENST00000335727.13	c.*10369A>G		3_prime_UTR_variant	Exon 21 of 21	1		ENSP00000338371.8
TNRC6B	ENST00000301923.13	c.*10369A>G		3_prime_UTR_variant	Exon 24 of 24	5		ENSP00000306759.9

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30150 AN: 151994 Hom.: 3534 Cov.: 31

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.215 AC: 89 AN: 414 Hom.: 12 Cov.: 0 AF XY: 0.224 AC XY: 55 AN XY: 246

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.220 AC: 87 AN: 396

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.143 AC: 2 AN: 14

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.198 AC: 30192 AN: 152112 Hom.: 3545 Cov.: 31 AF XY: 0.204 AC XY: 15189 AN XY: 74322

African (AFR) AF: 0.164 AC: 6798 AN: 41504

American (AMR) AF: 0.375 AC: 5735 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 384 AN: 3470

East Asian (EAS) AF: 0.256 AC: 1318 AN: 5156

South Asian (SAS) AF: 0.161 AC: 780 AN: 4832

European-Finnish (FIN) AF: 0.218 AC: 2309 AN: 10570

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12197 AN: 67984

Other (OTH) AF: 0.184 AC: 389 AN: 2110

Alfa AF: 0.192 Hom.: 11464

Bravo AF: 0.213

Asia WGS AF: 0.215 AC: 749 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.39
DANN	Benign	0.72
PhyloP100		-0.035
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: rs470113; hg19: chr22-40729614; COSMIC: COSV57308937;