11-68157911-C-G

Variant summary

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

The NM_017635.5(KMT5B):​c.2435G>C​(p.Arg812Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R812Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

KMT5B
NM_017635.5 missense

Scores

2
15

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.534
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]

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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=0.08752641).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KMT5BNM_017635.5 linkc.2435G>C p.Arg812Pro missense_variant Exon 11 of 11 ENST00000304363.9 NP_060105.3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KMT5BENST00000304363.9 linkc.2435G>C p.Arg812Pro missense_variant Exon 11 of 11 5 NM_017635.5 ENSP00000305899.4 Q4FZB7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461724
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727142
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Intellectual disability, autosomal dominant 51 Uncertain:1
Oct 09, 2023
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.073
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
16
DANN
Benign
0.97
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.63
FATHMM_MKL
Benign
0.33
N
LIST_S2
Uncertain
0.87
.;D
M_CAP
Benign
0.025
D
MetaRNN
Benign
0.088
T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-1.5
N;.
REVEL
Benign
0.15
Sift
Uncertain
0.0060
D;.
Sift4G
Benign
0.096
T;T
Vest4
0.27
MutPred
0.27
Gain of loop (P = 0.0166);Gain of loop (P = 0.0166);
MVP
0.093
MPC
0.73
ClinPred
0.54
D
GERP RS
-0.96
gMVP
0.30

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.

Other links and lift over

hg19: chr11-67925378; API