21-32576780-AC-A

Variant names:

• chr21-32576780-AC-A
• rs541034925
• NM_144659.7:c.641delG

Variant summary

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

The NM_144659.7(TCP10L):​c.641delG​(p.Gly214ValfsTer26) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,609,864 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: TCP10L NM_144659.7 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCP10L	NM_144659.7	c.641delG	p.Gly214ValfsTer26	frameshift_variant	Exon 5 of 5	ENST00000300258.8	NP_653260.1
CFAP298-TCP10L	NM_001350338.2	c.1163delG	p.Gly388ValfsTer26	frameshift_variant	Exon 8 of 8		NP_001337267.1
CFAP298-TCP10L	NR_146638.2	n.1297delG		non_coding_transcript_exon_variant	Exon 8 of 11
CFAP298-TCP10L	NR_146639.2	n.1297delG		non_coding_transcript_exon_variant	Exon 8 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCP10L	ENST00000300258.8	c.641delG	p.Gly214ValfsTer26	frameshift_variant	Exon 5 of 5	1	NM_144659.7	ENSP00000300258.3
CFAP298-TCP10L	ENST00000673807.1	c.1163delG	p.Gly388ValfsTer26	frameshift_variant	Exon 8 of 8			ENSP00000501088.1

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151628 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000151 AC: 22 AN: 1458236 Hom.: 0 Cov.: 32 AF XY: 0.0000221 AC XY: 16 AN XY: 725162

Gnomad4 AFR exome AF: 0.0000300

Gnomad4 AMR exome AF: 0.0000226

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000720

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151628 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74010

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs541034925; hg19: chr21-33949090;