rs199422280

Variant names:

• chr3-169764739-C-A
• rs199422280
• ENST00000602385.3:n.322G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-169764739-C-A
• chr3-169764739-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000602385.3(TERC):​n.322G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TERC ENST00000602385.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 0 publications found

Genes affected

TERC (HGNC:11727): (telomerase RNA component) Telomerase is a ribonucleoprotein polymerase that maintains telomere ends by addition of the telomere repeat TTAGGG. The enzyme consists of a protein component with reverse transcriptase activity, and an RNA component, encoded by this gene, that serves as a template for the telomere repeat. Telomerase expression plays a role in cellular senescence, as it is normally repressed in postnatal somatic cells resulting in progressive shortening of telomeres. Deregulation of telomerase expression in somatic cells may be involved in oncogenesis. Studies in mouse suggest that telomerase also participates in chromosomal repair, since de novo synthesis of telomere repeats may occur at double-stranded breaks. Mutations in this gene cause autosomal dominant dyskeratosis congenita, and may also be associated with some cases of aplastic anemia. [provided by RefSeq, Jul 2008]

TERC Gene-Disease associations (from GenCC):

• dyskeratosis congenita, autosomal dominant 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• acute myeloid leukemia

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

ENSG00000296372 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.14).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TERC	NR_001566.3	n.322G>T		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TERC	ENST00000602385.3	n.322G>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000296372	ENST00000738610.1	n.354C>A		non_coding_transcript_exon_variant	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 600490 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 327692

African (AFR) AF: 0.00 AC: 0 AN: 17354

American (AMR) AF: 0.00 AC: 0 AN: 42028

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20664

East Asian (EAS) AF: 0.00 AC: 0 AN: 35402

South Asian (SAS) AF: 0.00 AC: 0 AN: 68186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3900

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 343992

Other (OTH) AF: 0.00 AC: 0 AN: 32372

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.14
CADD	Benign	21
DANN	Benign	0.91
PhyloP100		1.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs199422280; hg19: chr3-169482527;