12-49020739-C-A

Position:

• chr12-49020739-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_003482.4(KMT2D):​c.*1041G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 210,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0014 (0 hom.)
• Consequence: KMT2D NM_003482.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.167

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 12-49020739-C-A is Benign according to our data. Variant chr12-49020739-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2642931.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 201 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KMT2D	NM_003482.4	c.*1041G>T		3_prime_UTR_variant	55/55	ENST00000301067.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KMT2D	ENST00000301067.12	c.*1041G>T		3_prime_UTR_variant	55/55	5	NM_003482.4	A2
KMT2D	ENST00000683543.2	c.*1041G>T		3_prime_UTR_variant	56/56			P4
KMT2D	ENST00000691932.1	c.*1041G>T		3_prime_UTR_variant	5/5
KMT2D	ENST00000685024.1	c.*1658G>T		3_prime_UTR_variant, NMD_transcript_variant	7/7

Frequencies

GnomAD3 genomes AF: 0.00132 AC: 201 AN: 151974 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00253

Gnomad OTH AF: 0.00192

GnomAD4 exome AF: 0.00143 AC: 83 AN: 58204 Hom.: 0 Cov.: 0 AF XY: 0.00169 AC XY: 46 AN XY: 27146

Gnomad4 AFR exome AF: 0.000824

Gnomad4 AMR exome AF: 0.00118

Gnomad4 ASJ exome AF: 0.000809

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00205

Gnomad4 OTH exome AF: 0.000842

GnomAD4 genome AF: 0.00132 AC: 201 AN: 152092 Hom.: 0 Cov.: 31 AF XY: 0.00130 AC XY: 97 AN XY: 74366

Gnomad4 AFR AF: 0.000482

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00253

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.00138 Hom.: 0

Bravo AF: 0.00134

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

KMT2D: BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	13
DANN	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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: rs563489548; hg19: chr12-49414522;