16-66788278-CAA-C

Variant names:

• chr16-66788278-CAA-C
• rs1308550551
• NM_001136505.2:c.289_290delTT

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001136505.2(TERB1):​c.289_290delTT​(p.Leu97ValfsTer7) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000149 in 1,343,218 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: TERB1 NM_001136505.2 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.40
• Publications: 1 publications found

Genes affected

TERB1 (HGNC:26675): (telomere repeat binding bouquet formation protein 1) Predicted to be involved in homologous chromosome pairing at meiosis and meiotic attachment of telomere to nuclear envelope. Predicted to be located in chromosome, telomeric region and nuclear inner membrane. Predicted to colocalize with shelterin complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-66788278-CAA-C is Pathogenic according to our data. Variant chr16-66788278-CAA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 1326959.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136505.2. 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
	TERB1	NM_001136505.2	MANE Select	c.289_290delTT	p.Leu97ValfsTer7	frameshift	Exon 6 of 19	NP_001129977.1	Q8NA31-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TERB1	ENST00000433154.6	TSL:5 MANE Select	c.289_290delTT	p.Leu97ValfsTer7	frameshift	Exon 6 of 19	ENSP00000463762.1	Q8NA31-1
	TERB1	ENST00000558713.6	TSL:5	c.289_290delTT	p.Leu97ValfsTer7	frameshift	Exon 5 of 18	ENSP00000462883.1	Q8NA31-1
	TERB1	ENST00000673664.1		c.256_257delTT	p.Leu86ValfsTer7	frameshift	Exon 6 of 12	ENSP00000500999.1	A0A669KAY0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000149 AC: 2 AN: 1343218 Hom.: 0 AF XY: 0.00000151 AC XY: 1 AN XY: 662114

African (AFR) AF: 0.00 AC: 0 AN: 27628

American (AMR) AF: 0.00 AC: 0 AN: 21058

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23722

East Asian (EAS) AF: 0.00 AC: 0 AN: 32804

South Asian (SAS) AF: 0.00 AC: 0 AN: 68772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48784

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5564

European-Non Finnish (NFE) AF: 0.00000189 AC: 2 AN: 1059160

Other (OTH) AF: 0.00 AC: 0 AN: 55726

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Spermatogenic failure 60 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.4

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: rs1308550551; hg19: chr16-66822181;