NM_144659.7:c.425A>C

Variant names:

• chr21-32578767-T-G
• rs1601122716
• NM_144659.7:c.425A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144659.7(TCP10L):​c.425A>C​(p.Tyr142Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 33)
• Consequence: TCP10L NM_144659.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.672

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]

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]

ACMG classification

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=0.09020001).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCP10L	NM_144659.7	c.425A>C	p.Tyr142Ser	missense_variant	Exon 4 of 5	ENST00000300258.8	NP_653260.1
CFAP298-TCP10L	NM_001350338.2	c.947A>C	p.Tyr316Ser	missense_variant	Exon 7 of 8		NP_001337267.1
CFAP298-TCP10L	NR_146638.2	n.1081A>C		non_coding_transcript_exon_variant	Exon 7 of 11
CFAP298-TCP10L	NR_146639.2	n.1081A>C		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	c.425A>C	p.Tyr142Ser	missense_variant	Exon 4 of 5	1	NM_144659.7	ENSP00000300258.3
CFAP298-TCP10L	ENST00000673807.1	c.947A>C	p.Tyr316Ser	missense_variant	Exon 7 of 8			ENSP00000501088.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	5.1
DANN	Benign	0.70
DEOGEN2	Benign	0.0047	T;.;.
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.0030	N
LIST_S2	Benign	0.53	T;T;T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.090	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;.;.
PROVEAN	Benign	-1.5	N;.;.
REVEL	Benign	0.073
Sift	Uncertain	0.012	D;.;.
Sift4G	Uncertain	0.015	D;D;.
Polyphen		0.94	P;.;.
Vest4		0.16
MutPred		0.29		Loss of catalytic residue at Y142 (P = 0.0285);.;Loss of catalytic residue at Y142 (P = 0.0285);
MVP		0.092
MPC		0.13
ClinPred		0.20	T
GERP RS		-0.77
Varity_R		0.18
gMVP		0.091

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

Other links and lift over

dbSNP: rs1601122716; hg19: chr21-33951077;