Genetic Variant NM_144659.7:c.370C>G (chr21-32578822-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_144659.7(TCP10L):c.370C>G(p.Pro124Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TCP10L
NM_144659.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.781

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:54636): (CFAP298-TCP10L readthrough) This locus represents naturally occurring readthrough transcription between the neighboring chromosome 21 open reading frame 59 (C21orf59) and TCP10L (t-complex 10 like) genes on chromosome 21. Readthrough transcripts may encode a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Apr 2017]

CFAP298-TCP10L links:

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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=0.059280515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCP10L	NM_144659.7 link	c.370C>G	p.Pro124Ala	missense_variant	Exon 4 of 5	ENST00000300258.8	NP_653260.1	Q8TDR4
CFAP298-TCP10L	NM_001350338.2 link	c.892C>G	p.Pro298Ala	missense_variant	Exon 7 of 8		NP_001337267.1
CFAP298-TCP10L	NR_146638.2 link	n.1026C>G		non_coding_transcript_exon_variant	Exon 7 of 11
CFAP298-TCP10L	NR_146639.2 link	n.1026C>G		non_coding_transcript_exon_variant	Exon 7 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCP10L	ENST00000300258.8 link	c.370C>G	p.Pro124Ala	missense_variant	Exon 4 of 5	1	NM_144659.7	ENSP00000300258.3		Q8TDR4
CFAP298-TCP10L	ENST00000673807.1 link	c.892C>G	p.Pro298Ala	missense_variant	Exon 7 of 8			ENSP00000501088.1		A0A669KAY3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727212

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:

0.00000270

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

0.077

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.93

DANN

Benign

0.53

DEOGEN2

Benign

0.0028

T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.56

T;T;T

M_CAP

Benign

0.0015

MetaRNN

Benign

0.059

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.4

L;.;.

PROVEAN

Benign

-1.1

N;.;.

REVEL

Benign

0.022

Sift

Benign

0.11

T;.;.

Sift4G

Benign

0.27

T;T;.

Polyphen

0.026

B;.;.

Vest4

0.13

MutPred

0.30

Gain of helix (P = 0.005);.;Gain of helix (P = 0.005);

MVP

0.030

MPC

0.070

ClinPred

0.085

GERP RS

-0.63

Varity_R

0.064

gMVP

0.023

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

Computational scores

Splicing

Publications

Other links and lift over