rs76663644

Variant names:

• chr12-49051605-G-A
• NM_003482.4:c.2078C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-49051605-G-A
• chr12-49051605-G-C
• chr12-49051605-G-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.2078C>T​(p.Pro693Leu) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KMT2D NM_003482.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02

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=0.18072733).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMT2D	NM_003482.4	c.2078C>T	p.Pro693Leu	missense_variant	Exon 11 of 55	ENST00000301067.12	NP_003473.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KMT2D	ENST00000301067.12	c.2078C>T	p.Pro693Leu	missense_variant	Exon 11 of 55	5	NM_003482.4	ENSP00000301067.7
KMT2D	ENST00000683543.2	c.2078C>T	p.Pro693Leu	missense_variant	Exon 11 of 56			ENSP00000506726.1
KMT2D	ENST00000685166.1	c.2078C>T	p.Pro693Leu	missense_variant	Exon 10 of 54			ENSP00000509386.1
KMT2D	ENST00000692637.1	c.2078C>T	p.Pro693Leu	missense_variant	Exon 10 of 54			ENSP00000509666.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.61	T
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	0.81	L
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D
Polyphen		0.0040	B
Vest4		0.42
MutPred		0.33		Loss of relative solvent accessibility (P = 0.0186);
MVP		0.25
MPC		0.19
ClinPred		0.19	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.34

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: chr12-49445388;