chr21-32576780-A-AC

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_144659.7(TCP10L):​c.641dupG​(p.Val215CysfsTer49) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000735 in 1,609,992 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00068 (4 hom.)
• Consequence: TCP10L NM_144659.7 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0760
• Publications: 2 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 21-32576780-A-AC is Benign according to our data. Variant chr21-32576780-A-AC is described in ClinVar as Benign. ClinVar VariationId is 724391.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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.641dupG	p.Val215CysfsTer49	frameshift	Exon 5 of 5	NP_653260.1	Q8TDR4
	CFAP298-TCP10L	NM_001350338.2		c.1163dupG	p.Val389CysfsTer49	frameshift	Exon 8 of 8	NP_001337267.1	A0A669KAY3
	CFAP298-TCP10L	NR_146638.2		n.1297dupG		non_coding_transcript_exon	Exon 8 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCP10L	ENST00000300258.8	TSL:1 MANE Select	c.641dupG	p.Val215CysfsTer49	frameshift	Exon 5 of 5	ENSP00000300258.3	Q8TDR4
	CFAP298-TCP10L	ENST00000673807.1		c.1163dupG	p.Val389CysfsTer49	frameshift	Exon 8 of 8	ENSP00000501088.1	A0A669KAY3
	CFAP298-TCP10L	ENST00000673945.1		c.947dupG	p.Val317CysfsTer49	frameshift	Exon 7 of 7	ENSP00000501020.1	A0A669KAW7

Frequencies

GnomAD3 genomes AF: 0.00131 AC: 198 AN: 151628 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.000339

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000833

Gnomad FIN AF: 0.0149

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00240

GnomAD2 exomes AF: 0.00166 AC: 408 AN: 246346 AF XY: 0.00152

Gnomad AFR exome AF: 0.000687

Gnomad AMR exome AF: 0.0000899

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0143

Gnomad NFE exome AF: 0.000625

Gnomad OTH exome AF: 0.00134

GnomAD4 exome AF: 0.000676 AC: 986 AN: 1458248 Hom.: 4 Cov.: 32 AF XY: 0.000641 AC XY: 465 AN XY: 725176

African (AFR) AF: 0.000541 AC: 18 AN: 33288

American (AMR) AF: 0.000158 AC: 7 AN: 44194

Ashkenazi Jewish (ASJ) AF: 0.0000769 AC: 2 AN: 26018

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39656

South Asian (SAS) AF: 0.000223 AC: 19 AN: 85336

European-Finnish (FIN) AF: 0.0135 AC: 720 AN: 53186

Middle Eastern (MID) AF: 0.000870 AC: 5 AN: 5750

European-Non Finnish (NFE) AF: 0.000148 AC: 164 AN: 1110580

Other (OTH) AF: 0.000830 AC: 50 AN: 60240

GnomAD4 genome AF: 0.00130 AC: 198 AN: 151744 Hom.: 4 Cov.: 33 AF XY: 0.00193 AC XY: 143 AN XY: 74136

African (AFR) AF: 0.000338 AC: 14 AN: 41362

American (AMR) AF: 0.00 AC: 0 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000834 AC: 4 AN: 4796

European-Finnish (FIN) AF: 0.0149 AC: 157 AN: 10530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 67874

Other (OTH) AF: 0.00238 AC: 5 AN: 2102

Alfa AF: 0.000727 Hom.: 0

Bravo AF: 0.000264

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.076
Mutation Taster		=189/11	polymorphism

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

Other links and lift over

dbSNP: rs541034925; hg19: chr21-33949090; COSMIC: COSV55828296; COSMIC: COSV55828296;