NM_017489.3:c.287A>T

Variant names:

• chr8-73009173-A-T
• rs762882340
• NM_017489.3:c.287A>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017489.3(TERF1):​c.287A>T​(p.Glu96Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TERF1 NM_017489.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

Genes affected

TERF1 (HGNC:11728): (telomeric repeat binding factor 1) This gene encodes a telomere specific protein which is a component of the telomere nucleoprotein complex. This protein is present at telomeres throughout the cell cycle and functions as an inhibitor of telomerase, acting in cis to limit the elongation of individual chromosome ends. The protein structure contains a C-terminal Myb motif, a dimerization domain near its N-terminus and an acidic N-terminus. Multiple transcripts of this gene are alternatively spliced products. [provided by RefSeq, Aug 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.370722).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TERF1	NM_017489.3	c.287A>T	p.Glu96Val	missense_variant	Exon 1 of 10	ENST00000276603.10	NP_059523.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TERF1	ENST00000276603.10	c.287A>T	p.Glu96Val	missense_variant	Exon 1 of 10	1	NM_017489.3	ENSP00000276603.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458700 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 725716

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Uncertain	0.66	D;.;.
Eigen	Benign	-0.090
Eigen_PC	Benign	-0.028
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.2	M;M;.
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.1	D;D;D
REVEL	Benign	0.16
Sift	Benign	0.13	T;T;D
Sift4G	Uncertain	0.021	D;D;D
Polyphen		0.60	P;B;.
Vest4		0.28
MutPred		0.55		Loss of disorder (P = 0.0155);Loss of disorder (P = 0.0155);Loss of disorder (P = 0.0155);
MVP		0.40
MPC		0.64
ClinPred		0.97	D
GERP RS		5.0
Varity_R		0.46
gMVP		0.25

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: rs762882340; hg19: chr8-73921408;