16-66767492-G-C

Variant names:

• chr16-66767492-G-C
• NM_001136505.2:c.1703C>G

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001136505.2(TERB1):​c.1703C>G​(p.Ser568*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TERB1 NM_001136505.2 stop_gained
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 0.998

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

Verdict is Pathogenic. Variant got 12 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 16-66767492-G-C is Pathogenic according to our data. Variant chr16-66767492-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 1244235.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TERB1	NM_001136505.2	c.1703C>G	p.Ser568*	stop_gained	Exon 16 of 19	ENST00000433154.6	NP_001129977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TERB1	ENST00000433154.6	c.1703C>G	p.Ser568*	stop_gained	Exon 16 of 19	5	NM_001136505.2	ENSP00000463762.1
TERB1	ENST00000558713.6	c.1703C>G	p.Ser568*	stop_gained	Exon 15 of 18	5		ENSP00000462883.1
TERB1	ENST00000313294.7	n.1512C>G		non_coding_transcript_exon_variant	Exon 14 of 16	5		ENSP00000464579.1
TERB1	ENST00000561333.1	n.1869C>G		non_coding_transcript_exon_variant	Exon 15 of 15	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Spermatogenic failure 60 Pathogenic:1

Dec 02, 2021

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Non-obstructive azoospermia Pathogenic:1

Aug 23, 2021

Institute of Reproductive Genetics, University of Münster

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.55	D
BayesDel_noAF	Pathogenic	0.55
CADD	Pathogenic	37
DANN	Uncertain	0.99
Eigen	Pathogenic	0.78
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Benign	0.69	D
Vest4		0.15
ClinPred		0.85	D
GERP RS		3.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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: chr16-66801395;