Variant chr6-35122123-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001370687.1(TCP11):c.572T>C(p.Leu191Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

TCP11
NM_001370687.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.48

Variant links:

Genes affected

TCP11 (HGNC:11658): (t-complex 11) Predicted to be involved in several processes, including protein kinase A signaling; regulation of cAMP-mediated signaling; and regulation of sperm capacitation. Located in acrosomal vesicle and sperm flagellum. [provided by Alliance of Genome Resources, Apr 2022]

TCP11 links:

TCP11 (HGNC:):

TCP11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.809

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCP11	NM_001370687.1 linkuse as main transcript	c.572T>C	p.Leu191Pro	missense_variant	5/10	ENST00000311875.11	NP_001357616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCP11	ENST00000311875.11 linkuse as main transcript	c.572T>C	p.Leu191Pro	missense_variant	5/10	1	NM_001370687.1	ENSP00000308708.6		Q8WWU5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251328

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135826

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Nov 15, 2024

The c.611T>C (p.L204P) alteration is located in exon 5 (coding exon 5) of the TCP11 gene. This alteration results from a T to C substitution at nucleotide position 611, causing the leucine (L) at amino acid position 204 to be replaced by a proline (P). 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

Pathogenic

0.78

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.10

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

.;.;.;.;.;.;.;T;.;.

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.81

T;.;T;T;T;T;T;T;.;T

M_CAP

Benign

0.021

MetaRNN

Pathogenic

0.81

D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.4

.;.;.;.;.;.;.;M;.;.

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-6.1

D;D;D;D;.;D;D;D;D;D

REVEL

Uncertain

0.42

Sift

Pathogenic

0.0

D;D;D;D;.;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;.

Polyphen

1.0, 1.0

.;D;.;.;.;D;.;D;.;.

Vest4

0.92

MutPred

0.64

.;.;.;.;.;.;.;Loss of stability (P = 0.0404);.;.;

MVP

0.32

MPC

0.76

ClinPred

0.98

GERP RS

4.2

Varity_R

0.94

gMVP

0.74

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

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