rs368471915

Variant names:

• chr12-49054623-C-A
• NM_003482.4:c.305G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-49054623-C-A
• chr12-49054623-C-G
• chr12-49054623-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.305G>T​(p.Ser102Ile) 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. 13/21 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: -1.07

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=0.093224734).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMT2D	NM_003482.4	c.305G>T	p.Ser102Ile	missense_variant	Exon 4 of 55	ENST00000301067.12	NP_003473.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KMT2D	ENST00000301067.12	c.305G>T	p.Ser102Ile	missense_variant	Exon 4 of 55	5	NM_003482.4	ENSP00000301067.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	9.8
DANN	Uncertain	0.98
DEOGEN2	Benign	0.052	T;T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.65	T;T
M_CAP	Pathogenic	0.37	D
MetaRNN	Benign	0.093	T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.9	N;D
REVEL	Benign	0.23
Sift	Uncertain	0.0030	D;D
Polyphen		0.21	B;.
Vest4		0.22
MutPred		0.23		Loss of glycosylation at S102 (P = 0.0143);Loss of glycosylation at S102 (P = 0.0143);
MVP		0.15
MPC		0.22
ClinPred		0.16	T
GERP RS		-0.26
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
Varity_R		0.14
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr12-49448406;