Variant 19-55346619-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032701.4(KMT5C):c.827G>A(p.Ser276Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000483 in 1,571,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

KMT5C
NM_032701.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.293

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.077056766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KMT5C	NM_032701.4 linkuse as main transcript	c.827G>A	p.Ser276Asn	missense_variant	8/9	ENST00000255613.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KMT5C	ENST00000255613.8 linkuse as main transcript	c.827G>A	p.Ser276Asn	missense_variant	8/9	1	NM_032701.4	P1	Q86Y97-1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000173

AC:

AN:

173282

Hom.:

AF XY:

0.0000106

AC XY:

AN XY:

94022

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000422

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000458

AC:

AN:

1419772

Hom.:

Cov.:

AF XY:

0.0000455

AC XY:

AN XY:

702628

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000586

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.000145

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:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.00000849

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2021

The c.827G>A (p.S276N) alteration is located in exon 8 (coding exon 7) of the KMT5C gene. This alteration results from a G to A substitution at nucleotide position 827, causing the serine (S) at amino acid position 276 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

Cadd

Benign

5.2

Dann

Benign

0.97

DEOGEN2

Benign

0.045

T;.

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.36

T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.077

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.65

PROVEAN

Benign

0.46

N;.

REVEL

Benign

0.042

Sift

Benign

0.098

T;.

Sift4G

Benign

0.066

T;D

Polyphen

0.079

B;.

Vest4

0.077

MutPred

0.15

Loss of phosphorylation at S276 (P = 0.0244);.;

MVP

0.15

MPC

0.47

ClinPred

0.058

GERP RS

0.79

Varity_R

0.030

gMVP

0.40

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