Variant 16-66770212-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001136505.2(TERB1):c.1370G>A(p.Arg457Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000747 in 1,552,098 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00078 ( 1 hom. )

Consequence

TERB1
NM_001136505.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.16

Variant links:

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]

TERB1 links:

TERB1 (HGNC:):

TERB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.018646747).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TERB1	NM_001136505.2 linkuse as main transcript	c.1370G>A	p.Arg457Gln	missense_variant	14/19	ENST00000433154.6	NP_001129977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TERB1	ENST00000433154.6 linkuse as main transcript	c.1370G>A	p.Arg457Gln	missense_variant	14/19	5	NM_001136505.2	ENSP00000463762.1	Q8NA31-1
TERB1	ENST00000558713.6 linkuse as main transcript	c.1370G>A	p.Arg457Gln	missense_variant	13/18	5		ENSP00000462883.1	Q8NA31-1
TERB1	ENST00000313294.7 linkuse as main transcript	n.1244G>A		non_coding_transcript_exon_variant	13/16	5		ENSP00000464579.1	Q8NA31-3
TERB1	ENST00000561333.1 linkuse as main transcript	n.1601G>A		non_coding_transcript_exon_variant	14/15	2

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000808

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000510

AC:

AN:

158864

Hom.:

AF XY:

0.000550

AC XY:

AN XY:

83664

show subpopulations

Gnomad AFR exome

AF:

0.000120

Gnomad AMR exome

AF:

0.000121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000527

Gnomad FIN exome

AF:

0.000762

Gnomad NFE exome

AF:

0.000823

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000778

AC:

1089

AN:

1399964

Hom.:

Cov.:

AF XY:

0.000771

AC XY:

532

AN XY:

690456

show subpopulations

Gnomad4 AFR exome

AF:

0.0000633

Gnomad4 AMR exome

AF:

0.0000840

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000416

Gnomad4 FIN exome

AF:

0.000606

Gnomad4 NFE exome

AF:

0.000912

Gnomad4 OTH exome

AF:

0.000636

GnomAD4 genome

AF:

0.000460

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000378

Gnomad4 NFE

AF:

0.000808

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000711

Hom.:

Bravo

AF:

0.000434

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000629

AC:

ExAC

AF:

0.000469

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.1370G>A (p.R457Q) alteration is located in exon 14 (coding exon 12) of the TERB1 gene. This alteration results from a G to A substitution at nucleotide position 1370, causing the arginine (R) at amino acid position 457 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.16

DANN

Benign

0.34

DEOGEN2

Benign

0.0015

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.43

.;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.019

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.19

REVEL

Benign

0.0090

Sift4G

Benign

0.23

T;T

Polyphen

0.53

P;P

Vest4

0.037

MVP

0.030

ClinPred

0.0037

GERP RS

-0.12

Varity_R

0.028

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over