rs201119371

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_003482.4(KMT2D):​c.13644C>T​(p.Ser4548=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00441 in 1,613,836 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0046 ( 26 hom. )

Consequence

KMT2D
NM_003482.4 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.0400
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
Variant 12-49030920-G-A is Benign according to our data. Variant chr12-49030920-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 94167.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-49030920-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.04 with no splicing effect.
BS2
High AC in GnomAd4 at 461 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KMT2DNM_003482.4 linkuse as main transcriptc.13644C>T p.Ser4548= synonymous_variant 41/55 ENST00000301067.12 NP_003473.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KMT2DENST00000301067.12 linkuse as main transcriptc.13644C>T p.Ser4548= synonymous_variant 41/555 NM_003482.4 ENSP00000301067 A2O14686-1

Frequencies

GnomAD3 genomes
AF:
0.00303
AC:
461
AN:
152186
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000724
Gnomad AMI
AF:
0.0121
Gnomad AMR
AF:
0.00111
Gnomad ASJ
AF:
0.00231
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00642
Gnomad FIN
AF:
0.00188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00497
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.00358
AC:
892
AN:
248816
Hom.:
4
AF XY:
0.00401
AC XY:
541
AN XY:
135052
show subpopulations
Gnomad AFR exome
AF:
0.000777
Gnomad AMR exome
AF:
0.00119
Gnomad ASJ exome
AF:
0.00129
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00667
Gnomad FIN exome
AF:
0.00121
Gnomad NFE exome
AF:
0.00517
Gnomad OTH exome
AF:
0.00215
GnomAD4 exome
AF:
0.00455
AC:
6655
AN:
1461532
Hom.:
26
Cov.:
38
AF XY:
0.00473
AC XY:
3441
AN XY:
727040
show subpopulations
Gnomad4 AFR exome
AF:
0.000657
Gnomad4 AMR exome
AF:
0.00110
Gnomad4 ASJ exome
AF:
0.00130
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00706
Gnomad4 FIN exome
AF:
0.00188
Gnomad4 NFE exome
AF:
0.00504
Gnomad4 OTH exome
AF:
0.00379
GnomAD4 genome
AF:
0.00303
AC:
461
AN:
152304
Hom.:
1
Cov.:
32
AF XY:
0.00291
AC XY:
217
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.000722
Gnomad4 AMR
AF:
0.00111
Gnomad4 ASJ
AF:
0.00231
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00643
Gnomad4 FIN
AF:
0.00188
Gnomad4 NFE
AF:
0.00497
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00429
Hom.:
1
Bravo
AF:
0.00288
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.00458
EpiControl
AF:
0.00344

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
Benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoMay 21, 2018- -
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Jun 18, 2014- -
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided Benign:3
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesOct 26, 2023- -
Benign, criteria provided, single submitterclinical testingGeneDxJan 18, 2019- -
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJun 01, 2024KMT2D: BP4, BP7, BS1, BS2 -
Kabuki syndrome Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 29, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
CADD
Benign
8.4
DANN
Benign
0.69
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs201119371; hg19: chr12-49424703; COSMIC: COSV56413108; COSMIC: COSV56413108; API