Variant 19-55347431-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032701.4(KMT5C):c.1371C>T(p.Val457Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00347 in 1,546,976 control chromosomes in the GnomAD database, including 169 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 85 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 84 hom. )

Consequence

KMT5C
NM_032701.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.883

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 Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 19-55347431-C-T is Benign according to our data. Variant chr19-55347431-C-T is described in ClinVar as [Benign]. Clinvar id is 769054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.883 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KMT5C	NM_032701.4 linkuse as main transcript	c.1371C>T	p.Val457Val	synonymous_variant	9/9	ENST00000255613.8	NP_116090.2	Q86Y97-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KMT5C	ENST00000255613.8 linkuse as main transcript	c.1371C>T	p.Val457Val	synonymous_variant	9/9	1	NM_032701.4	ENSP00000255613.3	Q86Y97-1
KMT5C	ENST00000630497.1 linkuse as main transcript	c.1026C>T	p.Val342Val	synonymous_variant	7/7	1		ENSP00000486397.1	A0A0D9SF94
KMT5C	ENST00000445196.5 linkuse as main transcript	n.*911C>T		non_coding_transcript_exon_variant	8/8	5		ENSP00000397296.1	Q86Y97-2
KMT5C	ENST00000445196.5 linkuse as main transcript	n.*911C>T		3_prime_UTR_variant	8/8	5		ENSP00000397296.1	Q86Y97-2

Frequencies

GnomAD3 genomes

AF:

0.0177

AC:

2695

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0621

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00563

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00521

AC:

950

AN:

182370

Hom.:

AF XY:

0.00396

AC XY:

399

AN XY:

100756

show subpopulations

Gnomad AFR exome

AF:

0.0654

Gnomad AMR exome

AF:

0.00396

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000613

Gnomad SAS exome

AF:

0.000142

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000197

Gnomad OTH exome

AF:

0.00202

GnomAD4 exome

AF:

0.00191

AC:

2665

AN:

1394782

Hom.:

Cov.:

AF XY:

0.00166

AC XY:

1142

AN XY:

688928

show subpopulations

Gnomad4 AFR exome

AF:

0.0680

Gnomad4 AMR exome

AF:

0.00410

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000154

Gnomad4 SAS exome

AF:

0.000218

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000756

Gnomad4 OTH exome

AF:

0.00395

GnomAD4 genome

AF:

0.0178

AC:

2706

AN:

152194

Hom.:

Cov.:

AF XY:

0.0163

AC XY:

1213

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0622

Gnomad4 AMR

AF:

0.00562

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00799

Hom.:

Bravo

AF:

0.0206

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 24, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

3.0

DANN

Benign

0.78

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