rs757243017

Variant names:

• chr19-10137944-C-A
• NM_001130823.3:c.4181G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-10137944-C-A
• chr19-10137944-C-T

Variant summary

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

The NM_001130823.3(DNMT1):​c.4181G>T​(p.Arg1394Leu) variant causes a missense change. 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: 33)
• Consequence: DNMT1 NM_001130823.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.74

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 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
DNMT1	NM_001130823.3	c.4181G>T	p.Arg1394Leu	missense_variant	Exon 36 of 41	ENST00000359526.9	NP_001124295.1
DNMT1	NM_001318730.2	c.4133G>T	p.Arg1378Leu	missense_variant	Exon 35 of 40		NP_001305659.1
DNMT1	NM_001379.4	c.4133G>T	p.Arg1378Leu	missense_variant	Exon 35 of 40		NP_001370.1
DNMT1	NM_001318731.2	c.3818G>T	p.Arg1273Leu	missense_variant	Exon 36 of 41		NP_001305660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNMT1	ENST00000359526.9	c.4181G>T	p.Arg1394Leu	missense_variant	Exon 36 of 41	1	NM_001130823.3	ENSP00000352516.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.88	D;.
Eigen	Benign	0.099
Eigen_PC	Benign	0.094
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.075	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-4.2	D;D
REVEL	Uncertain	0.53
Sift	Benign	0.11	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.80	P;P
Vest4		0.53
MutPred		0.53		Loss of disorder (P = 0.0538);.;
MVP		0.83
MPC		1.7
ClinPred		0.98	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.61
gMVP		0.81

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-10248620;