16-66759258-G-C

Variant names:

• chr16-66759258-G-C
• rs963945421
• NM_001136505.2:c.1813C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001136505.2(TERB1):​c.1813C>G​(p.Arg605Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000719 in 1,391,738 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: TERB1 NM_001136505.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.63

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TERB1	NM_001136505.2	c.1813C>G	p.Arg605Gly	missense_variant	Exon 17 of 19	ENST00000433154.6	NP_001129977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TERB1	ENST00000433154.6	c.1813C>G	p.Arg605Gly	missense_variant	Exon 17 of 19	5	NM_001136505.2	ENSP00000463762.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1391738 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 686016

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.28e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.33
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T;T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.75	.;T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Uncertain	0.53	T
REVEL	Uncertain	0.57
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.41
MutPred		0.53		Loss of stability (P = 0.0049);Loss of stability (P = 0.0049);
MVP		0.44
ClinPred		0.91	D
GERP RS		4.6
Varity_R		0.74
gMVP		0.50

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: rs963945421; hg19: chr16-66793161;