chr16-2039907-C-CCAGAGCCATGCGGCCAT

Position:

• chr16-2039907-C-CCAGAGCCATGCGGCCAT

Variant summary

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

The NM_002528.7(NTHL1):​c.913_*16dupATGGCCGCATGGCTCTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NTHL1 NM_002528.7 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.86

Genes affected

NTHL1 (HGNC:8028): (nth like DNA glycosylase 1) The protein encoded by this gene is a DNA N-glycosylase of the endonuclease III family. Like a similar protein in E. coli, the encoded protein has DNA glycosylase activity on DNA substrates containing oxidized pyrimidine residues and has apurinic/apyrimidinic lyase activity. [provided by RefSeq, Oct 2008]

NTHL1 (HGNC:):

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/exons	MANE	Protein	UniProt
NTHL1	NM_002528.7	c.913_*16dupATGGCCGCATGGCTCTG		3_prime_UTR_variant	6/6	ENST00000651570.2	NP_002519.2
NTHL1	NM_001318193.2	c.742_*16dupATGGCCGCATGGCTCTG		3_prime_UTR_variant	5/5		NP_001305122.2
NTHL1	NM_001318194.2	c.583_*16dupATGGCCGCATGGCTCTG		3_prime_UTR_variant	6/6		NP_001305123.1
NTHL1	XM_047434171.1	c.634_*16dupATGGCCGCATGGCTCTG		3_prime_UTR_variant	6/6		XP_047290127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTHL1	ENST00000651570	c.913_*16dupATGGCCGCATGGCTCTG		3_prime_UTR_variant	6/6		NM_002528.7	ENSP00000498421.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary cancer-predisposing syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2024

The c.939_*16dup17 variant results from a duplication of 17 nucleotides at positions c.939 to c.*16 at the 3' end of the NTHL1 gene. This nucleotide region is generally well conserved in available vertebrate species. Based on the available evidence, the clinical significance of this variant remains unclear. -

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: chr16-2089908;