Variant chr12-49034136-T-C 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.10671A>G(p.Pro3557Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0594 in 1,613,254 control chromosomes in the GnomAD database, including 3,267 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.042 ( 174 hom., cov: 32)

Exomes 𝑓: 0.061 ( 3093 hom. )

Consequence

KMT2D
NM_003482.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -3.90

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=-0.78).

BP6

Variant 12-49034136-T-C is Benign according to our data. Variant chr12-49034136-T-C is described in ClinVar as [Benign]. Clinvar id is 94138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-49034136-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.9 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KMT2D	NM_003482.4 linkuse as main transcript	c.10671A>G	p.Pro3557Pro	synonymous_variant	39/55	ENST00000301067.12	NP_003473.3	O14686-1Q59FG6Q6PIA1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KMT2D	ENST00000301067.12 linkuse as main transcript	c.10671A>G	p.Pro3557Pro	synonymous_variant	39/55	5	NM_003482.4	ENSP00000301067.7		O14686-1

Frequencies

GnomAD3 genomes

AF:

0.0423

AC:

6436

AN:

152154

Hom.:

174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0118

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.0427

Gnomad ASJ

AF:

0.0757

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0128

Gnomad FIN

AF:

0.0435

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0631

Gnomad OTH

AF:

0.0468

GnomAD3 exomes

AF:

0.0462

AC:

11489

AN:

248740

Hom.:

382

AF XY:

0.0463

AC XY:

6245

AN XY:

134990

show subpopulations

Gnomad AFR exome

AF:

0.00988

Gnomad AMR exome

AF:

0.0366

Gnomad ASJ exome

AF:

0.0826

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.0166

Gnomad FIN exome

AF:

0.0451

Gnomad NFE exome

AF:

0.0655

Gnomad OTH exome

AF:

0.0630

GnomAD4 exome

AF:

0.0612

AC:

89441

AN:

1460982

Hom.:

3093

Cov.:

AF XY:

0.0599

AC XY:

43500

AN XY:

726788

show subpopulations

Gnomad4 AFR exome

AF:

0.00995

Gnomad4 AMR exome

AF:

0.0393

Gnomad4 ASJ exome

AF:

0.0798

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0172

Gnomad4 FIN exome

AF:

0.0458

Gnomad4 NFE exome

AF:

0.0701

Gnomad4 OTH exome

AF:

0.0555

GnomAD4 genome

AF:

0.0423

AC:

6437

AN:

152272

Hom.:

174

Cov.:

AF XY:

0.0412

AC XY:

3066

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0118

Gnomad4 AMR

AF:

0.0426

Gnomad4 ASJ

AF:

0.0757

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0130

Gnomad4 FIN

AF:

0.0435

Gnomad4 NFE

AF:

0.0631

Gnomad4 OTH

AF:

0.0464

Alfa

AF:

0.0574

Hom.:

158

Bravo

AF:

0.0431

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 20, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Kabuki syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.59

DANN

Benign

0.58

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