Genetic Variant TCP11:p.Ala153Thr (chr6-35122238-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001370687.1(TCP11):c.457G>A(p.Ala153Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TCP11
NM_001370687.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.56

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40735304).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCP11	NM_001370687.1 link	c.457G>A	p.Ala153Thr	missense_variant	Exon 5 of 10	ENST00000311875.11	NP_001357616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCP11	ENST00000311875.11 link	c.457G>A	p.Ala153Thr	missense_variant	Exon 5 of 10	1	NM_001370687.1	ENSP00000308708.6		Q8WWU5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727248

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

3.7

DANN

Benign

0.90

DEOGEN2

Benign

0.014

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

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.69

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

M_CAP

Benign

0.0063

MetaRNN

Benign

0.41

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.9

.;.;.;.;.;.;.;L;.;.;.

PrimateAI

Benign

0.22

PROVEAN

Uncertain

-3.2

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

REVEL

Benign

0.077

Sift

Benign

0.033

D;D;D;D;.;D;D;D;D;D;T

Sift4G

Uncertain

0.024

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

Polyphen

0.0010, 0.030

.;B;.;.;.;B;.;B;.;.;.

Vest4

0.024

MutPred

0.73

.;.;.;.;.;.;.;Loss of ubiquitination at K155 (P = 0.1079);.;.;.;

MVP

0.061

MPC

0.16

ClinPred

0.45

GERP RS

1.5

Varity_R

0.074

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over