chr22-40056115-T-C

Variant names:

• chr22-40056115-T-C
• rs9623117
• ENST00000402203.5:c.-121+10527T>C

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_001024843.2(TNRC6B):c.-121+11117T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. Note: NM_001024843.2 is not a MANE Select or MANE Plus Clinical transcript for TNRC6B; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The variant allele was found at a cumulative frequency of 0.368 (AC=55,958) in the gnomAD database across 152,086 control chromosomes, including 15,089 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.758. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (15089 hom., cov: 32)
• Consequence: TNRC6B NM_001024843.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 1 publications found

Genes affected

TNRC6B (HGNC:29190): (trinucleotide repeat containing adaptor 6B) Enables RNA binding activity. Involved in positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; positive regulation of nuclear-transcribed mRNA poly(A) tail shortening; and regulatory ncRNA-mediated gene silencing. Acts upstream of with a positive effect on miRNA-mediated gene silencing by inhibition of translation. 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, Jul 2025]

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: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Benign. The variant received -12 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.7581 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001024843.2. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	TNRC6B NM_001024843.2		c.-121+11117T>C	intron	Intron 1 of 23	Prot: NP_001020014.1 UniProt:

TNRC6B NM_001024843.2

HGVSc / HGVSpc.-121+11117T>C

Exon rankIntron 1 of 23

intron

Prot: NP_001020014.1UniProt: Q9UPQ9-2

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	TNRC6B ENST00000402203.5	TSL:1	c.-121+10527T>C	intron	Intron 1 of 23	Prot: ENSP00000384795.1 UniProt:
	TNRC6B ENST00000301923.13	TSL:5	c.-121+11117T>C	intron	Intron 1 of 23	Prot: ENSP00000306759.9 UniProt:

TNRC6B ENST00000402203.5

TSL:1

HGVSc / HGVSpc.-121+10527T>C

Exon rankIntron 1 of 23

intron

Prot: ENSP00000384795.1UniProt: Q9UPQ9-2

TNRC6B ENST00000301923.13

TSL:5

HGVSc / HGVSpc.-121+11117T>C

Exon rankIntron 1 of 23

intron

Prot: ENSP00000306759.9UniProt: Q9UPQ9-2

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.368	AC:55852	Hom:15035	AN:151968	Cov:32
GnomAD4 genome	AF: 0.368	AC:55958	Hom:15089	AN:152086	Cov:32
TOPMed (Bravo)	AF: 0.383	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.263	AC:154294	Hom:27179	AN:587204	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.303	AC:710	Hom:136	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.0392	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.203	AC:61	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.235	AC:818	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.0410	AC:298	Hom:	AN:7232	Cov:
Qatari Genome	AF: 0.375	AC:66	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.0317	AC:3891	Hom:77	AN:122692	Cov:
Turkish Variome	AF: 0.268	AC:415	Hom:65	AN:1546	Cov:
UK10K	AF: 0.229	AC:1734	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.0317	AC:284	Hom:3	AN:8960	Cov:

Showing 14 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	2.1
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.19
DANN	Benign	0.42
GPN-Star LLR	N/A	4.3
GPN-Star score	N/A	-0.092
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	-2.0

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0

Showing 1 of 1 scores

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs9623117;

hg19: chr22-40452119;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar