NM_144659.7:c.433_435delCACinsAGA

Variant names:

• chr21-32578757-GTG-TCT
• NM_144659.7:c.433_435delCACinsAGA
• TCP10L p.His145Arg

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_144659.7(TCP10L):​c.433_435delCACinsAGA​(p.His145Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TCP10L NM_144659.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.336
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144659.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCP10L	NM_144659.7	MANE Select	c.433_435delCACinsAGA	p.His145Arg	missense	N/A	NP_653260.1	Q8TDR4
	CFAP298-TCP10L	NM_001350338.2		c.955_957delCACinsAGA	p.His319Arg	missense	N/A	NP_001337267.1	A0A669KAY3
	CFAP298-TCP10L	NR_146638.2		n.1089_1091delCACinsAGA		non_coding_transcript_exon	Exon 7 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCP10L	ENST00000300258.8	TSL:1 MANE Select	c.433_435delCACinsAGA	p.His145Arg	missense	N/A	ENSP00000300258.3	Q8TDR4
	CFAP298-TCP10L	ENST00000673807.1		c.955_957delCACinsAGA	p.His319Arg	missense	N/A	ENSP00000501088.1	A0A669KAY3
	CFAP298-TCP10L	ENST00000673985.1		c.955_957delCACinsAGA	p.His319Arg	missense	N/A	ENSP00000500984.1	A0A669KAW9

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.34

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr21-33951067;