Variant 11-68157725-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_017635.5(KMT5B):c.2621G>A(p.Arg874Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

KMT5B
NM_017635.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.38

Variant links:

Genes affected

KMT5B (HGNC:24283): (lysine methyltransferase 5B) This gene encodes a protein that contains a SET domain. SET domains appear to be protein-protein interaction domains that mediate interactions with a family of proteins that display similarity with dual-specificity phosphatases (dsPTPases). The function of this gene has not been determined. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

KMT5B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), KMT5B. . Gene score misZ 2.7894 (greater than the threshold 3.09). Trascript score misZ 3.742 (greater than threshold 3.09). GenCC has associacion of gene with complex neurodevelopmental disorder, intellectual disability, autosomal dominant 51.

BP4

Computational evidence support a benign effect (MetaRNN=0.2789403).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KMT5B	NM_017635.5 linkuse as main transcript	c.2621G>A	p.Arg874Lys	missense_variant	11/11	ENST00000304363.9	NP_060105.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KMT5B	ENST00000304363.9 linkuse as main transcript	c.2621G>A	p.Arg874Lys	missense_variant	11/11	5	NM_017635.5	ENSP00000305899	P1	Q4FZB7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1449976

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720178

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:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 12, 2021

The c.2621G>A (p.R874K) alteration is located in exon 11 (coding exon 10) of the KMT5B gene. This alteration results from a G to A substitution at nucleotide position 2621, causing the arginine (R) at amino acid position 874 to be replaced by a lysine (K). 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

Pathogenic

0.89

BayesDel_addAF

Uncertain

0.021

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

.;D

M_CAP

Benign

0.057

MetaRNN

Benign

0.28

T;T

MetaSVM

Benign

-0.37

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.84

N;.

REVEL

Benign

0.24

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.21

T;T

Vest4

0.36

MutPred

0.40

Gain of ubiquitination at R874 (P = 0.0048);Gain of ubiquitination at R874 (P = 0.0048);

MVP

0.15

MPC

0.86

ClinPred

0.97

GERP RS

5.0

gMVP

0.39

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over