rs10420321

chr19-10189741-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001130823.3(DNMT1):c.80+5079T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 151,956 control chromosomes in the GnomAD database, including 1,504 homozygotes. 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: 𝑓 0.12 (1504 hom., cov: 31)
• Consequence: DNMT1 NM_001130823.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.488

Genes affected

DNMT1 (HGNC:2976): (DNA methyltransferase 1) This gene encodes an enzyme that transfers methyl groups to cytosine nucleotides of genomic DNA. This protein is the major enzyme responsible for maintaining methylation patterns following DNA replication and shows a preference for hemi-methylated DNA. Methylation of DNA is an important component of mammalian epigenetic gene regulation. Aberrant methylation patterns are found in human tumors and associated with developmental abnormalities. Variation in this gene has been associated with cerebellar ataxia, deafness, and narcolepsy, and neuropathy, hereditary sensory, type IE. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNMT1	NM_001130823.3	c.80+5079T>C		intron_variant		ENST00000359526.9
DNMT1	NM_001318730.2	c.80+5079T>C		intron_variant
DNMT1	NM_001318731.2	c.-244+5079T>C		intron_variant
DNMT1	NM_001379.4	c.80+5079T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNMT1	ENST00000359526.9	c.80+5079T>C		intron_variant		1	NM_001130823.3

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17802 AN: 151838 Hom.: 1499 Cov.: 31

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.0926

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0628

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.117 AC: 17850 AN: 151956 Hom.: 1504 Cov.: 31 AF XY: 0.123 AC XY: 9129 AN XY: 74264

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.0926

Gnomad4 NFE AF: 0.0628

Gnomad4 OTH AF: 0.112

Alfa AF: 0.0806 Hom.: 85

Bravo AF: 0.127

Asia WGS AF: 0.264 AC: 920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	3.9
Dann	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs10420321; hg19: chr19-10300417;