12-49039623-CAA-CA

Variant names:

• chr12-49039623-CA-C
• rs200754433
• NM_003482.4:c.8047-7delT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_003482.4(KMT2D):​c.8047-7delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000369 in 1,599,036 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: KMT2D NM_003482.4 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.08

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 12-49039623-CA-C is Benign according to our data. Variant chr12-49039623-CA-C is described in ClinVar as [Benign]. Clinvar id is 2086095.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-49039623-CA-C is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAdExome4 at 57 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMT2D	NM_003482.4	c.8047-7delT		splice_region_variant, intron_variant	Intron 32 of 54	ENST00000301067.12	NP_003473.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KMT2D	ENST00000301067.12	c.8047-7delT		splice_region_variant, intron_variant	Intron 32 of 54	5	NM_003482.4	ENSP00000301067.7

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151712 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000394 AC: 57 AN: 1447324 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 29 AN XY: 719904

Gnomad4 AFR exome AF: 0.0000610

Gnomad4 AMR exome AF: 0.0000708

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000105

Gnomad4 NFE exome AF: 0.0000406

Gnomad4 OTH exome AF: 0.0000334

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151712 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74070

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000295

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000227

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Kabuki syndrome Benign:1

Dec 25, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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: rs200754433; hg19: chr12-49433406;