chr22-40301577-C-T

Variant names:

• chr22-40301577-C-T
• rs139909
• NM_001162501.2:c.4120+244C>T

Variant summary

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

The NM_001162501.2(TNRC6B):​c.4120+244C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 503,550 control chromosomes in the GnomAD database, including 118,721 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 0.73 (41847 hom., cov: 31)
  • Exomes 𝑓: 0.66 (76874 hom.)
• Consequence: TNRC6B NM_001162501.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472
• Publications: 24 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 (AFR) allele frequency at 95% confidence interval = 0.919 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.4120+244C>T		intron	N/A	NP_001155973.1
	TNRC6B	NM_015088.3		c.3790+244C>T		intron	N/A	NP_055903.2
	TNRC6B	NM_001024843.2		c.1708+244C>T		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.4120+244C>T		intron	N/A	ENSP00000401946.2
	TNRC6B	ENST00000335727.13	TSL:1	c.3790+244C>T		intron	N/A	ENSP00000338371.8
	TNRC6B	ENST00000446273.1	TSL:1	c.3175+244C>T		intron	N/A	ENSP00000409429.1

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110702 AN: 151714 Hom.: 41778 Cov.: 31

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.668

GnomAD4 exome AF: 0.658 AC: 231487 AN: 351720 Hom.: 76874 AF XY: 0.664 AC XY: 121577 AN XY: 183070

African (AFR) AF: 0.920 AC: 9305 AN: 10112

American (AMR) AF: 0.694 AC: 8635 AN: 12440

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 7079 AN: 11456

East Asian (EAS) AF: 0.451 AC: 11282 AN: 25034

South Asian (SAS) AF: 0.800 AC: 24423 AN: 30538

European-Finnish (FIN) AF: 0.610 AC: 13812 AN: 22630

Middle Eastern (MID) AF: 0.613 AC: 1016 AN: 1658

European-Non Finnish (NFE) AF: 0.656 AC: 142137 AN: 216724

Other (OTH) AF: 0.653 AC: 13798 AN: 21128

GnomAD4 genome AF: 0.730 AC: 110831 AN: 151830 Hom.: 41847 Cov.: 31 AF XY: 0.725 AC XY: 53834 AN XY: 74208

African (AFR) AF: 0.927 AC: 38436 AN: 41480

American (AMR) AF: 0.672 AC: 10230 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2173 AN: 3464

East Asian (EAS) AF: 0.432 AC: 2221 AN: 5138

South Asian (SAS) AF: 0.801 AC: 3859 AN: 4818

European-Finnish (FIN) AF: 0.614 AC: 6471 AN: 10532

Middle Eastern (MID) AF: 0.592 AC: 173 AN: 292

European-Non Finnish (NFE) AF: 0.666 AC: 45237 AN: 67874

Other (OTH) AF: 0.667 AC: 1401 AN: 2100

Alfa AF: 0.682 Hom.: 158101

Bravo AF: 0.740

Asia WGS AF: 0.680 AC: 2364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.80
DANN	Benign	0.18
PhyloP100		-0.47
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: rs139909; hg19: chr22-40697581;