NM_017489.3:c.285C>T

Variant names:

• chr8-73009171-C-T
• rs56288812
• NM_017489.3:c.285C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_017489.3(TERF1):​c.285C>T​(p.Ser95Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00294 in 1,610,894 control chromosomes in the GnomAD database, including 132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (70 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (62 hom.)
• Consequence: TERF1 NM_017489.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.651
• Publications: 1 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 8-73009171-C-T is Benign according to our data. Variant chr8-73009171-C-T is described in ClinVar as Benign. ClinVar VariationId is 1272980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.651 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017489.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TERF1	NM_017489.3	MANE Select	c.285C>T	p.Ser95Ser	synonymous	Exon 1 of 10	NP_059523.2	P54274-1
	TERF1	NM_001413365.1		c.-104C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	NP_001400294.1
	TERF1	NM_001413366.1		c.-104C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_001400295.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TERF1	ENST00000276603.10	TSL:1 MANE Select	c.285C>T	p.Ser95Ser	synonymous	Exon 1 of 10	ENSP00000276603.5	P54274-1
	TERF1	ENST00000276602.10	TSL:1	c.285C>T	p.Ser95Ser	synonymous	Exon 1 of 9	ENSP00000276602.6	P54274-2
	TERF1	ENST00000899325.1		c.285C>T	p.Ser95Ser	synonymous	Exon 1 of 11	ENSP00000569384.1

Frequencies

GnomAD3 genomes AF: 0.0157 AC: 2391 AN: 152186 Hom.: 70 Cov.: 33

Gnomad AFR AF: 0.0534

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00818

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0143

GnomAD2 exomes AF: 0.00389 AC: 934 AN: 240134 AF XY: 0.00290

Gnomad AFR exome AF: 0.0574

Gnomad AMR exome AF: 0.00244

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000103

Gnomad OTH exome AF: 0.00286

GnomAD4 exome AF: 0.00160 AC: 2339 AN: 1458590 Hom.: 62 Cov.: 33 AF XY: 0.00134 AC XY: 969 AN XY: 725666

African (AFR) AF: 0.0558 AC: 1864 AN: 33428

American (AMR) AF: 0.00296 AC: 132 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51548

Middle Eastern (MID) AF: 0.00226 AC: 11 AN: 4864

European-Non Finnish (NFE) AF: 0.0000756 AC: 84 AN: 1111840

Other (OTH) AF: 0.00382 AC: 230 AN: 60258

GnomAD4 genome AF: 0.0158 AC: 2402 AN: 152304 Hom.: 70 Cov.: 33 AF XY: 0.0149 AC XY: 1107 AN XY: 74476

African (AFR) AF: 0.0536 AC: 2226 AN: 41558

American (AMR) AF: 0.00816 AC: 125 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68028

Other (OTH) AF: 0.0142 AC: 30 AN: 2114

Alfa AF: 0.00460 Hom.: 2

Bravo AF: 0.0184

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.6
DANN	Benign	0.94
PhyloP100		-0.65
PromoterAI		0.033	Neutral
Mutation Taster		=100/0	polymorphism

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: rs56288812; hg19: chr8-73921406;