rs55834252

Variant names:

• chr8-73024967-T-A
• rs55834252
• NM_017489.3:c.770T>A

Your query was ambiguous. Multiple possible variants found:

• chr8-73024967-T-A
• chr8-73024967-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_017489.3(TERF1):​c.770T>A​(p.Met257Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TERF1 NM_017489.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.808

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TERF1	NM_017489.3	c.770T>A	p.Met257Lys	missense_variant	Exon 5 of 10	ENST00000276603.10	NP_059523.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TERF1	ENST00000276603.10	c.770T>A	p.Met257Lys	missense_variant	Exon 5 of 10	1	NM_017489.3	ENSP00000276603.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000445 AC: 1 AN: 224650 AF XY: 0.00000813

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399444 Hom.: 0 Cov.: 26 AF XY: 0.00000143 AC XY: 1 AN XY: 698570

African (AFR) AF: 0.00 AC: 0 AN: 31970

American (AMR) AF: 0.00 AC: 0 AN: 39704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25574

East Asian (EAS) AF: 0.00 AC: 0 AN: 39022

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 81962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39692

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5640

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1077312

Other (OTH) AF: 0.00 AC: 0 AN: 58568

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Pathogenic	0.22
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.57	D;.;T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Pathogenic	0.81	D;D;D
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.3	M;M;.
PhyloP100		2.9
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.2	D;D;D
REVEL	Benign	0.29
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0090	D;D;D
Polyphen		0.81	P;P;.
Vest4		0.78
MutPred		0.79		Gain of disorder (P = 0.0174);Gain of disorder (P = 0.0174);.;
MVP		0.62
MPC		0.70
ClinPred		0.94	D
GERP RS		5.8
Varity_R		0.89
gMVP		0.49
Mutation Taster		=50/50

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

Other links and lift over

dbSNP: rs55834252; hg19: chr8-73937202;