rs1555196013

Variant names:

• chr12-49049790-C-A
• rs1555196013
• NM_003482.4:c.3798G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-49049790-C-A
• chr12-49049790-C-G
• chr12-49049790-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003482.4(KMT2D):​c.3798G>T​(p.Glu1266Asp) variant causes a missense 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KMT2D NM_003482.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.51

Genes affected

KMT2D (HGNC:7133): (lysine methyltransferase 2D) The protein encoded by this gene is a histone methyltransferase that methylates the Lys-4 position of histone H3. The encoded protein is part of a large protein complex called ASCOM, which has been shown to be a transcriptional regulator of the beta-globin and estrogen receptor genes. Mutations in this gene have been shown to be a cause of Kabuki syndrome. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17628795).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMT2D	NM_003482.4	c.3798G>T	p.Glu1266Asp	missense_variant	Exon 12 of 55	ENST00000301067.12	NP_003473.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KMT2D	ENST00000301067.12	c.3798G>T	p.Glu1266Asp	missense_variant	Exon 12 of 55	5	NM_003482.4	ENSP00000301067.7
KMT2D	ENST00000683543.2	c.3798G>T	p.Glu1266Asp	missense_variant	Exon 12 of 56			ENSP00000506726.1
KMT2D	ENST00000685166.1	c.3798G>T	p.Glu1266Asp	missense_variant	Exon 11 of 54			ENSP00000509386.1
KMT2D	ENST00000692637.1	c.3798G>T	p.Glu1266Asp	missense_variant	Exon 11 of 54			ENSP00000509666.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Seizure;C0334083:Connective tissue nevi Uncertain:1

Jan 01, 2017

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.041	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.18	T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Benign	1.5	L
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.92	N
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D
Polyphen		0.26	B
Vest4		0.30
MutPred		0.10		Gain of helix (P = 0.0854);
MVP		0.52
MPC		0.32
ClinPred		0.67	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1555196013; hg19: chr12-49443573;