15-44973888-AAC-A

Position:

• chr15-44973888-AAC-A

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_152448.3(TERB2):​c.457_458del​(p.Thr153SerfsTer17) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TERB2 NM_152448.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.57

Genes affected

TERB2 (HGNC:28520): (telomere repeat binding bouquet formation protein 2) 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. Predicted to be active in nuclear inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Pathogenic. Variant got 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 15-44973888-AAC-A is Pathogenic according to our data. Variant chr15-44973888-AAC-A is described in ClinVar as [Pathogenic]. Clinvar id is 1326957.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TERB2	NM_152448.3	c.457_458del	p.Thr153SerfsTer17	frameshift_variant	6/7	ENST00000340827.4	NP_689661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TERB2	ENST00000340827.4	c.457_458del	p.Thr153SerfsTer17	frameshift_variant	6/7	1	NM_152448.3	ENSP00000340644	P1
TERB2	ENST00000557864.1	c.*361_*362del		3_prime_UTR_variant, NMD_transcript_variant	4/6	3		ENSP00000452951
TERB2	ENST00000559137.5	c.*423_*424del		3_prime_UTR_variant, NMD_transcript_variant	5/6	5		ENSP00000454013

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

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Spermatogenic failure 59 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 02, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.31		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.31		Position offset: -21

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-45266086;