8-73008948-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_017489.3(TERF1):​c.62C>T​(p.Ala21Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,612,782 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

TERF1
NM_017489.3 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.530
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.054491222).
BS2
High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TERF1NM_017489.3 linkuse as main transcriptc.62C>T p.Ala21Val missense_variant 1/10 ENST00000276603.10 NP_059523.2 P54274-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TERF1ENST00000276603.10 linkuse as main transcriptc.62C>T p.Ala21Val missense_variant 1/101 NM_017489.3 ENSP00000276603.5 P54274-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152224
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000162
AC:
4
AN:
246642
Hom.:
0
AF XY:
0.0000150
AC XY:
2
AN XY:
133604
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000292
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000548
Gnomad SAS exome
AF:
0.0000330
Gnomad FIN exome
AF:
0.0000465
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1460440
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
726418
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000448
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:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152342
Hom.:
0
Cov.:
33
AF XY:
0.0000268
AC XY:
2
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000251
Hom.:
0
Bravo
AF:
0.0000151
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsSep 16, 2021The c.62C>T (p.A21V) alteration is located in exon 1 (coding exon 1) of the TERF1 gene. This alteration results from a C to T substitution at nucleotide position 62, causing the alanine (A) at amino acid position 21 to be replaced by a valine (V). 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
0.12
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
18
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.50
D;.;.
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.59
FATHMM_MKL
Benign
0.11
N
LIST_S2
Uncertain
0.88
D;D;D
M_CAP
Benign
0.0057
T
MetaRNN
Benign
0.054
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.4
M;M;.
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-1.1
N;N;N
REVEL
Benign
0.11
Sift
Uncertain
0.0060
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
0.98
D;D;.
Vest4
0.18
MVP
0.30
MPC
0.18
ClinPred
0.21
T
GERP RS
3.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.12
gMVP
0.17

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

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

Other links and lift over

dbSNP: rs370999354; hg19: chr8-73921183; COSMIC: COSV52577923; COSMIC: COSV52577923; API