NM_018319.4:c.-276_-274delCCG

Variant names:

• chr14-89955920-GGCC-G
• NM_018319.4:c.-276_-274delCCG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018319.4(TDP1):​c.-276_-274delCCG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TDP1 NM_018319.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.523

Genes affected

TDP1 (HGNC:18884): (tyrosyl-DNA phosphodiesterase 1) The protein encoded by this gene is involved in repairing stalled topoisomerase I-DNA complexes by catalyzing the hydrolysis of the phosphodiester bond between the tyrosine residue of topoisomerase I and the 3-prime phosphate of DNA. This protein may also remove glycolate from single-stranded DNA containing 3-prime phosphoglycolate, suggesting a role in repair of free-radical mediated DNA double-strand breaks. This gene is a member of the phospholipase D family and contains two PLD phosphodiesterase domains. Mutations in this gene are associated with the disease spinocerebellar ataxia with axonal neuropathy (SCAN1). [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDP1	NM_018319.4	c.-276_-274delCCG		5_prime_UTR_variant	Exon 1 of 17	ENST00000335725.9	NP_060789.2
TDP1	NM_018319.4	c.-276_-274delCCG		non_coding_transcript_variant		ENST00000335725.9	NP_060789.2
TDP1	NM_018319.4	c.-280_-278delGCC		upstream_gene_variant		ENST00000335725.9	NP_060789.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDP1	ENST00000335725	c.-276_-274delCCG		5_prime_UTR_variant	Exon 1 of 17	1	NM_018319.4	ENSP00000337353.4
TDP1	ENST00000335725.9	c.-276_-274delCCG		non_coding_transcript_variant		1	NM_018319.4	ENSP00000337353.4
TDP1	ENST00000335725.9	c.-280_-278delGCC		upstream_gene_variant		1	NM_018319.4	ENSP00000337353.4

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-90422264;