Variant 12-49033869-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003482.4(KMT2D):c.10836G>A(p.Gln3612Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 1,554,972 control chromosomes in the GnomAD database, including 122,526 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14131 hom., cov: 32)

Exomes 𝑓: 0.39 ( 108395 hom. )

Consequence

KMT2D
NM_003482.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.772

Variant links:

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]

KMT2D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 12-49033869-C-T is Benign according to our data. Variant chr12-49033869-C-T is described in ClinVar as [Benign]. Clinvar id is 94142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-49033869-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.772 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KMT2D	NM_003482.4 link	c.10836G>A	p.Gln3612Gln	synonymous_variant	40/55	ENST00000301067.12	NP_003473.3	O14686-1Q59FG6Q6PIA1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KMT2D	ENST00000301067.12 link	c.10836G>A	p.Gln3612Gln	synonymous_variant	40/55	5	NM_003482.4	ENSP00000301067.7		O14686-1

Frequencies

GnomAD3 genomes

AF:

0.424

AC:

64289

AN:

151758

Hom.:

14094

Cov.:

show subpopulations

Gnomad AFR

AF:

0.535

Gnomad AMI

AF:

0.355

Gnomad AMR

AF:

0.342

Gnomad ASJ

AF:

0.247

Gnomad EAS

AF:

0.425

Gnomad SAS

AF:

0.457

Gnomad FIN

AF:

0.413

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.385

Gnomad OTH

AF:

0.383

GnomAD3 exomes

AF:

0.388

AC:

65517

AN:

168956

Hom.:

13087

AF XY:

0.391

AC XY:

35121

AN XY:

89764

show subpopulations

Gnomad AFR exome

AF:

0.537

Gnomad AMR exome

AF:

0.280

Gnomad ASJ exome

AF:

0.261

Gnomad EAS exome

AF:

0.440

Gnomad SAS exome

AF:

0.444

Gnomad FIN exome

AF:

0.415

Gnomad NFE exome

AF:

0.385

Gnomad OTH exome

AF:

0.368

GnomAD4 exome

AF:

0.390

AC:

546756

AN:

1403094

Hom.:

108395

Cov.:

AF XY:

0.390

AC XY:

270282

AN XY:

693142

show subpopulations

Gnomad4 AFR exome

AF:

0.542

Gnomad4 AMR exome

AF:

0.284

Gnomad4 ASJ exome

AF:

0.260

Gnomad4 EAS exome

AF:

0.396

Gnomad4 SAS exome

AF:

0.435

Gnomad4 FIN exome

AF:

0.412

Gnomad4 NFE exome

AF:

0.387

Gnomad4 OTH exome

AF:

0.392

GnomAD4 genome

AF:

0.424

AC:

64385

AN:

151878

Hom.:

14131

Cov.:

AF XY:

0.422

AC XY:

31357

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.536

Gnomad4 AMR

AF:

0.342

Gnomad4 ASJ

AF:

0.247

Gnomad4 EAS

AF:

0.424

Gnomad4 SAS

AF:

0.457

Gnomad4 FIN

AF:

0.413

Gnomad4 NFE

AF:

0.385

Gnomad4 OTH

AF:

0.382

Alfa

AF:

0.380

Hom.:

10850

Bravo

AF:

0.416

Asia WGS

AF:

0.439

AC:

1525

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 06, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 58% of patients studied by a panel of primary immunodeficiencies. Number of patients: 55. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 07, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Kabuki syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Kabuki syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Aug 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.40

DANN

Benign

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over