22-40251193-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4BP6_ModerateBS1BS2

The NM_001162501.2(TNRC6B):c.108A>C(p.Lys36Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000383 in 1,535,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00040 ( 0 hom. )

Consequence

TNRC6B
NM_001162501.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.21

Publications

2 publications found

Variant links:

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

TNRC6B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.28448594).

BP6

Variant 22-40251193-A-C is Benign according to our data. Variant chr22-40251193-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3026122.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00021 (32/152172) while in subpopulation NFE AF = 0.000294 (20/68042). AF 95% confidence interval is 0.000194. There are 0 homozygotes in GnomAd4. There are 10 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 32 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNRC6B	NM_001162501.2 link	c.108A>C	p.Lys36Asn	missense_variant	Exon 3 of 23	ENST00000454349.7	NP_001155973.1	Q9UPQ9-3
TNRC6B	NM_015088.3 link	c.108A>C	p.Lys36Asn	missense_variant	Exon 3 of 21		NP_055903.2	Q9UPQ9-1
TNRC6B	NM_001024843.2 link	c.216A>C	p.Lys72Asn	missense_variant	Exon 6 of 24		NP_001020014.1	Q9UPQ9-2A0A024R1N5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TNRC6B	ENST00000454349.7 link	c.108A>C	p.Lys36Asn	missense_variant	Exon 3 of 23	2	NM_001162501.2	ENSP00000401946.2	Q9UPQ9-3
TNRC6B	ENST00000335727.13 link	c.108A>C	p.Lys36Asn	missense_variant	Exon 3 of 21	1		ENSP00000338371.8	Q9UPQ9-1
TNRC6B	ENST00000402203.5 link	c.216A>C	p.Lys72Asn	missense_variant	Exon 6 of 24	1		ENSP00000384795.1	Q9UPQ9-2
TNRC6B	ENST00000301923.13 link	c.216A>C	p.Lys72Asn	missense_variant	Exon 6 of 24	5		ENSP00000306759.9	Q9UPQ9-2

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000121

AC:

AN:

148536

AF XY:

0.000101

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000291

Gnomad OTH exome

AF:

0.000240

GnomAD4 exome

AF:

0.000402

AC:

556

AN:

1383542

Hom.:

Cov.:

AF XY:

0.000357

AC XY:

244

AN XY:

682714

show subpopulations

African (AFR)

AF:

0.0000324

AC:

AN:

30836

American (AMR)

AF:

0.00

AC:

AN:

34254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24914

East Asian (EAS)

AF:

0.00

AC:

AN:

35558

South Asian (SAS)

AF:

0.00

AC:

AN:

77466

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48050

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4716

European-Non Finnish (NFE)

AF:

0.000479

AC:

513

AN:

1070500

Other (OTH)

AF:

0.000734

AC:

AN:

57248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.404

Heterozygous variant carriers

100

125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000210

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41432

American (AMR)

AF:

0.00

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

68042

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000358

Hom.:

Bravo

AF:

0.000246

ExAC

AF:

0.0000366

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

TNRC6B: BP1, BS1:Supporting -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

.;.;T;.

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.95

D;.;D;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.28

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.2

.;.;M;M

PhyloP100

6.2

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.050

N;N;N;N

REVEL

Benign

0.11

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Benign

0.44

T;T;D;D

Polyphen

0.99

D;D;D;D

Vest4

0.52

MutPred

0.30

.;.;Loss of methylation at K36 (P = 7e-04);Loss of methylation at K36 (P = 7e-04);

MVP

0.42

MPC

0.17

ClinPred

0.20

GERP RS

5.7

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.26

gMVP

0.22

Mutation Taster

=38/62

disease causing

(source)

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

Publications

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22-40251193-A-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over