Genetic Variant KMT5B:p.Arg187Arg (chr11-68173898-G-T) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_017635.5(KMT5B):c.559C>A(p.Arg187Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.00306 in 1,604,508 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 39 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 38 hom. )

Consequence

KMT5B
NM_017635.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.83

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 Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 11-68173898-G-T is Benign according to our data. Variant chr11-68173898-G-T is described in ClinVar as [Benign]. Clinvar id is 778540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.013 (1931/149044) while in subpopulation AFR AF= 0.0415 (1693/40784). AF 95% confidence interval is 0.0399. There are 39 homozygotes in gnomad4. There are 906 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1931 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMT5B	NM_017635.5 link	c.559C>A	p.Arg187Arg	synonymous_variant	Exon 6 of 11	ENST00000304363.9	NP_060105.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KMT5B	ENST00000304363.9 link	c.559C>A	p.Arg187Arg	synonymous_variant	Exon 6 of 11	5	NM_017635.5	ENSP00000305899.4		Q4FZB7-1

Frequencies

GnomAD3 genomes

AF:

0.0129

AC:

1927

AN:

148924

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0415

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00798

Gnomad ASJ

AF:

0.00522

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000221

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00641

Gnomad NFE

AF:

0.00120

Gnomad OTH

AF:

0.0104

GnomAD3 exomes

AF:

0.00437

AC:

1080

AN:

246914

Hom.:

AF XY:

0.00365

AC XY:

488

AN XY:

133584

show subpopulations

Gnomad AFR exome

AF:

0.0423

Gnomad AMR exome

AF:

0.00369

Gnomad ASJ exome

AF:

0.00859

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000101

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00137

Gnomad OTH exome

AF:

0.00531

GnomAD4 exome

AF:

0.00204

AC:

2972

AN:

1455464

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

1362

AN XY:

724308

show subpopulations

Gnomad4 AFR exome

AF:

0.0398

Gnomad4 AMR exome

AF:

0.00427

Gnomad4 ASJ exome

AF:

0.00856

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000105

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000777

Gnomad4 OTH exome

AF:

0.00522

GnomAD4 genome

AF:

0.0130

AC:

1931

AN:

149044

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

906

AN XY:

72428

show subpopulations

Gnomad4 AFR

AF:

0.0415

Gnomad4 AMR

AF:

0.00796

Gnomad4 ASJ

AF:

0.00522

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000221

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00120

Gnomad4 OTH

AF:

0.0103

Alfa

AF:

0.00734

Hom.:

Bravo

AF:

0.0151

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00196

EpiControl

AF:

0.00190

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

KMT5B: BP4, BP7, BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

KMT5B-related disorder

Benign:1

Jan 20, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

7.2

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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