Variant chr21-32582229-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144659.7(TCP10L):c.331C>G(p.Pro111Ala) 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 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TCP10L
NM_144659.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.898

Variant links:

Genes affected

TCP10L (HGNC:11657): (t-complex 10 like) Enables several functions, including identical protein binding activity; protein self-association; and transcription corepressor activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TCP10L links:

CFAP298-TCP10L (HGNC:):

CFAP298-TCP10L links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.076744795).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TCP10L	NM_144659.7 linkuse as main transcript	c.331C>G	p.Pro111Ala	missense_variant	3/5	ENST00000300258.8	NP_653260.1
CFAP298-TCP10L	NR_146638.2 linkuse as main transcript	n.987C>G		non_coding_transcript_exon_variant	6/11
CFAP298-TCP10L	NM_001350338.2 linkuse as main transcript	c.853C>G	p.Pro285Ala	missense_variant	6/8		NP_001337267.1
CFAP298-TCP10L	NR_146639.2 linkuse as main transcript	n.987C>G		non_coding_transcript_exon_variant	6/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCP10L	ENST00000300258.8 linkuse as main transcript	c.331C>G	p.Pro111Ala	missense_variant	3/5	1	NM_144659.7	ENSP00000300258	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727234

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

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 10, 2024

The c.331C>G (p.P111A) alteration is located in exon 3 (coding exon 2) of the TCP10L gene. This alteration results from a C to G substitution at nucleotide position 331, causing the proline (P) at amino acid position 111 to be replaced by an alanine (A). 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

0.081

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

4.3

DANN

Benign

0.74

DEOGEN2

Benign

0.0063

T;.;.;.

Eigen

Benign

-0.72

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.72

T;T;T;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.077

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.;.;.

MutationTaster

Benign

1.0

PROVEAN

Uncertain

-2.4

N;.;.;N

REVEL

Benign

0.084

Sift

Benign

0.099

T;.;.;D

Sift4G

Pathogenic

0.0

D;D;.;T

Polyphen

1.0

D;.;.;.

Vest4

0.14

MutPred

0.14

.;.;.;Loss of loop (P = 0.0512);

MVP

0.072

MPC

0.18

ClinPred

0.17

GERP RS

-0.54

Varity_R

0.067

gMVP

0.034

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over