Variant 12-106321517-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000299045.8(TCP11L2):c.446A>G(p.Asn149Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

TCP11L2
ENST00000299045.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.37

Variant links:

Genes affected

TCP11L2 (HGNC:28627): (t-complex 11 like 2) Predicted to be involved in signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

TCP11L2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055229545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCP11L2	NM_152772.3 linkuse as main transcript	c.446A>G	p.Asn149Ser	missense_variant	5/10	ENST00000299045.8	NP_689985.1	Q8N4U5-1A0A024RBH4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TCP11L2	ENST00000299045.8 linkuse as main transcript	c.446A>G	p.Asn149Ser	missense_variant	5/10	1	NM_152772.3	ENSP00000299045.3	Q8N4U5-1
TCP11L2	ENST00000546625.5 linkuse as main transcript	c.446A>G	p.Asn149Ser	missense_variant	5/6	1		ENSP00000449123.1	G3V1Z2
TCP11L2	ENST00000547153.5 linkuse as main transcript	c.446A>G	p.Asn149Ser	missense_variant	5/7	2		ENSP00000448952.1	Q8N4U5-2
TCP11L2	ENST00000553098.5 linkuse as main transcript	c.446A>G	p.Asn149Ser	missense_variant	6/7	5		ENSP00000448629.1	F8VRQ3

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000477

AC:

AN:

251328

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1461852

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000842

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2023

The c.446A>G (p.N149S) alteration is located in exon 5 (coding exon 4) of the TCP11L2 gene. This alteration results from a A to G substitution at nucleotide position 446, causing the asparagine (N) at amino acid position 149 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0060

.;T;.;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.078

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.81

T;T;T;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.055

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.48

N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.33

T;T;T;T

Sift4G

Benign

0.48

T;T;T;T

Polyphen

0.25, 0.037

.;B;B;.

Vest4

0.28

MutPred

0.49

Gain of phosphorylation at N149 (P = 0.1018);Gain of phosphorylation at N149 (P = 0.1018);Gain of phosphorylation at N149 (P = 0.1018);Gain of phosphorylation at N149 (P = 0.1018);

MVP

0.18

MPC

0.12

ClinPred

0.14

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over