21-32576780-A-AC

Position:

• chr21-32576780-A-AC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_144659.7(TCP10L):​c.641_642insG​(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

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:):

ACMG classification

Verdict is Likely_benign. Variant got -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 id is 724391.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCP10L	NM_144659.7	c.641_642insG	p.Val215CysfsTer49	frameshift_variant	5/5	ENST00000300258.8	NP_653260.1
CFAP298-TCP10L	NR_146638.2	n.1297_1298insG		non_coding_transcript_exon_variant	8/11
CFAP298-TCP10L	NM_001350338.2	c.1163_1164insG	p.Val389CysfsTer49	frameshift_variant	8/8		NP_001337267.1
CFAP298-TCP10L	NR_146639.2	n.1297_1298insG		non_coding_transcript_exon_variant	8/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCP10L	ENST00000300258.8	c.641_642insG	p.Val215CysfsTer49	frameshift_variant	5/5	1	NM_144659.7	ENSP00000300258	P1

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

GnomAD3 exomes AF: 0.00166 AC: 408 AN: 246346 Hom.: 2 AF XY: 0.00152 AC XY: 203 AN XY: 133252

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 SAS exome AF: 0.000306

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

Gnomad4 AFR exome AF: 0.000541

Gnomad4 AMR exome AF: 0.000158

Gnomad4 ASJ exome AF: 0.0000769

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000223

Gnomad4 FIN exome AF: 0.0135

Gnomad4 NFE exome AF: 0.000148

Gnomad4 OTH exome AF: 0.000830

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

Gnomad4 AFR AF: 0.000338

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000834

Gnomad4 FIN AF: 0.0149

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.00238

Bravo AF: 0.000264

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2018

- -

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;