14-20376224-C-G

Variant names:

• chr14-20376224-C-G
• rs2228042
• NM_007110.5:c.6129G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007110.5(TEP1):​c.6129G>C​(p.Thr2043Thr) variant causes a synonymous 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)
• Consequence: TEP1 NM_007110.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.39
• Publications: 10 publications found

Genes affected

TEP1 (HGNC:11726): (telomerase associated protein 1) This gene product is a component of the ribonucleoprotein complex responsible for telomerase activity which catalyzes the addition of new telomeres on the chromosome ends. The telomerase-associated proteins are conserved from ciliates to humans. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007110.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEP1	NM_007110.5	MANE Select	c.6129G>C	p.Thr2043Thr	synonymous	Exon 42 of 55	NP_009041.2
	TEP1	NM_001319035.2		c.5805G>C	p.Thr1935Thr	synonymous	Exon 40 of 53	NP_001305964.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEP1	ENST00000262715.10	TSL:1 MANE Select	c.6129G>C	p.Thr2043Thr	synonymous	Exon 42 of 55	ENSP00000262715.5
	TEP1	ENST00000556935.5	TSL:1	c.5805G>C	p.Thr1935Thr	synonymous	Exon 40 of 53	ENSP00000452574.1
	TEP1	ENST00000555008.5	TSL:1	n.4158G>C		non_coding_transcript_exon	Exon 30 of 43	ENSP00000450541.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.078
DANN	Benign	0.49
PhyloP100		-4.4

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: rs2228042; hg19: chr14-20844383;