Variant 19-55342738-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_032701.4(KMT5C):c.277-4C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.005 in 1,566,120 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0052 ( 27 hom. )

Consequence

KMT5C
NM_032701.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001262

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0800

Variant links:

Genes affected

KMT5C (HGNC:28405): (lysine methyltransferase 5C) SUV420H2 and the related enzyme SUV420H1 (MIM 610881) function as histone methyltransferases that specifically trimethylate nucleosomal histone H4 (see MIM 602822) on lysine-20 (K20) (Schotta et al., 2004 [PubMed 15145825]).[supplied by OMIM, Dec 2009]

KMT5C links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 19-55342738-C-A is Benign according to our data. Variant chr19-55342738-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2650518.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
KMT5C	NM_032701.4 linkuse as main transcript	c.277-4C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000255613.8
KMT5C	XM_006723442.4 linkuse as main transcript	c.-69-4C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
KMT5C	XM_011527415.4 linkuse as main transcript	c.277-4C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
KMT5C	XM_047439555.1 linkuse as main transcript	c.-69-4C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KMT5C	ENST00000255613.8 linkuse as main transcript	c.277-4C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_032701.4	P1	Q86Y97-1

Frequencies

GnomAD3 genomes

AF:

0.00321

AC:

488

AN:

151944

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00102

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00566

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00320

AC:

803

AN:

250662

Hom.:

AF XY:

0.00295

AC XY:

400

AN XY:

135700

show subpopulations

Gnomad AFR exome

AF:

0.000987

Gnomad AMR exome

AF:

0.00150

Gnomad ASJ exome

AF:

0.00428

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.000324

Gnomad NFE exome

AF:

0.00580

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00519

AC:

7339

AN:

1414058

Hom.:

Cov.:

AF XY:

0.00507

AC XY:

3578

AN XY:

706346

show subpopulations

Gnomad4 AFR exome

AF:

0.000957

Gnomad4 AMR exome

AF:

0.00181

Gnomad4 ASJ exome

AF:

0.00414

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000305

Gnomad4 FIN exome

AF:

0.000600

Gnomad4 NFE exome

AF:

0.00633

Gnomad4 OTH exome

AF:

0.00481

GnomAD4 genome

AF:

0.00321

AC:

488

AN:

152062

Hom.:

Cov.:

AF XY:

0.00270

AC XY:

201

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00566

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00465

Hom.:

Bravo

AF:

0.00337

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00551

EpiControl

AF:

0.00605

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

KMT5C: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

6.7

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00013

dbscSNV1_RF

Benign

0.014

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