19-55347206-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032701.4(KMT5C):c.1146C>A(p.Ala382=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00752 in 1,539,466 control chromosomes in the GnomAD database, including 720 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.039 (373 hom., cov: 33)
  • Exomes 𝑓: 0.0041 (347 hom.)
• Consequence: KMT5C NM_032701.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.788

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 19-55347206-C-A is Benign according to our data. Variant chr19-55347206-C-A is described in ClinVar as [Benign]. Clinvar id is 769053.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KMT5C	NM_032701.4	c.1146C>A	p.Ala382=	synonymous_variant	9/9	ENST00000255613.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KMT5C	ENST00000255613.8	c.1146C>A	p.Ala382=	synonymous_variant	9/9	1	NM_032701.4	P1
KMT5C	ENST00000630497.1	c.801C>A	p.Ala267=	synonymous_variant	7/7	1
KMT5C	ENST00000474492.1	n.716C>A		non_coding_transcript_exon_variant	3/3	2
KMT5C	ENST00000445196.5	c.*686C>A		3_prime_UTR_variant, NMD_transcript_variant	8/8	5

Frequencies

GnomAD3 genomes AF: 0.0387 AC: 5883 AN: 152170 Hom.: 372 Cov.: 33

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0157

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0273

GnomAD3 exomes AF: 0.00833 AC: 1120 AN: 134424 Hom.: 56 AF XY: 0.00678 AC XY: 498 AN XY: 73408

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.00666

Gnomad ASJ exome AF: 0.000370

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000221

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000382

Gnomad OTH exome AF: 0.00542

GnomAD4 exome AF: 0.00410 AC: 5683 AN: 1387178 Hom.: 347 Cov.: 32 AF XY: 0.00360 AC XY: 2464 AN XY: 684630

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.00848

Gnomad4 ASJ exome AF: 0.000239

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000253

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000173

Gnomad4 OTH exome AF: 0.0101

GnomAD4 genome AF: 0.0387 AC: 5899 AN: 152288 Hom.: 373 Cov.: 33 AF XY: 0.0370 AC XY: 2752 AN XY: 74462

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.0156

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000471

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.0122 Hom.: 33

Bravo AF: 0.0454

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	1.4
Dann	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs10420654; hg19: chr19-55858574; COSMIC: COSV55319662; COSMIC: COSV55319662;