rs1058511

chr19-55348071-C-Achr19-55348071-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_032701.4(KMT5C):c.*622C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,634 control chromosomes in the GnomAD database, including 16,802 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.46 (16754 hom., cov: 33)
  • Exomes 𝑓: 0.42 (48 hom.)
• Consequence: KMT5C NM_032701.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KMT5C	NM_032701.4	c.*622C>A		3_prime_UTR_variant	9/9	ENST00000255613.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KMT5C	ENST00000255613.8	c.*622C>A		3_prime_UTR_variant	9/9	1	NM_032701.4	P1
KMT5C	ENST00000630497.1	c.*622C>A		3_prime_UTR_variant	7/7	1
KMT5C	ENST00000445196.5	c.*1551C>A		3_prime_UTR_variant, NMD_transcript_variant	8/8	5

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70375 AN: 152016 Hom.: 16724 Cov.: 33

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.458

GnomAD4 exome AF: 0.418 AC: 208 AN: 498 Hom.: 48 Cov.: 0 AF XY: 0.429 AC XY: 132 AN XY: 308

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.423

Gnomad4 NFE exome AF: 0.320

Gnomad4 OTH exome AF: 0.583

GnomAD4 genome AF: 0.463 AC: 70449 AN: 152136 Hom.: 16754 Cov.: 33 AF XY: 0.469 AC XY: 34857 AN XY: 74368

Gnomad4 AFR AF: 0.505

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.737

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.453

Alfa AF: 0.424 Hom.: 28951

Bravo AF: 0.467

Asia WGS AF: 0.570 AC: 1985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
Cadd	Benign	7.9
Dann	Benign	0.89

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

Other links and lift over

dbSNP: rs1058511; hg19: chr19-55859439;