rs138039

Variant names:

• chr22-40225284-G-A
• rs138039
• NM_001162501.2:c.6-20731G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-40225284-G-A
• chr22-40225284-G-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.6-20731G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,012 control chromosomes in the GnomAD database, including 9,577 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 0.32 (9577 hom., cov: 32)
• Consequence: TNRC6B NM_001162501.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141
• Publications: 9 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), G2P, Ambry Genetics, PanelApp Australia
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNRC6B	NM_001162501.2	MANE Select	c.6-20731G>A		intron	N/A	NP_001155973.1	Q9UPQ9-3
	TNRC6B	NM_015088.3		c.6-20731G>A		intron	N/A	NP_055903.2	Q9UPQ9-1
	TNRC6B	NM_001024843.2		c.114-20731G>A		intron	N/A	NP_001020014.1	Q9UPQ9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNRC6B	ENST00000454349.7	TSL:2 MANE Select	c.6-20731G>A		intron	N/A	ENSP00000401946.2	Q9UPQ9-3
	TNRC6B	ENST00000335727.13	TSL:1	c.6-20731G>A		intron	N/A	ENSP00000338371.8	Q9UPQ9-1
	TNRC6B	ENST00000402203.5	TSL:1	c.114-20731G>A		intron	N/A	ENSP00000384795.1	Q9UPQ9-2

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48745 AN: 151892 Hom.: 9575 Cov.: 32

Gnomad AFR AF: 0.0954

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.321 AC: 48744 AN: 152012 Hom.: 9577 Cov.: 32 AF XY: 0.323 AC XY: 23982 AN XY: 74280

African (AFR) AF: 0.0954 AC: 3958 AN: 41510

American (AMR) AF: 0.373 AC: 5699 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1479 AN: 3470

East Asian (EAS) AF: 0.568 AC: 2924 AN: 5148

South Asian (SAS) AF: 0.252 AC: 1213 AN: 4812

European-Finnish (FIN) AF: 0.404 AC: 4266 AN: 10550

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27897 AN: 67942

Other (OTH) AF: 0.396 AC: 834 AN: 2106

Alfa AF: 0.375 Hom.: 8081

Bravo AF: 0.311

Asia WGS AF: 0.343 AC: 1192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.0
DANN	Benign	0.28
PhyloP100		-0.14
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: rs138039; hg19: chr22-40621288;