12-123409283-C-T

Variant names:

• chr12-123409283-C-T
• rs16917496
• NM_020382.7:c.*1580C>T

Variant summary

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

The NM_020382.7(KMT5A):​c.*1580C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 152,496 control chromosomes in the GnomAD database, including 27,183 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 0.55 (27072 hom., cov: 32)
  • Exomes 𝑓: 0.72 (111 hom.)
• Consequence: KMT5A NM_020382.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110

Genes affected

KMT5A (HGNC:29489): (lysine methyltransferase 5A) The protein encoded by this gene is a protein-lysine N-methyltransferase that can monomethylate Lys-20 of histone H4 to effect transcriptional repression of some genes. The encoded protein is required for cell proliferation and plays a role in chromatin condensation. [provided by RefSeq, May 2016]

RILPL2 (HGNC:28787): (Rab interacting lysosomal protein like 2) This gene encodes a protein that contains a rab-interacting lysosomal protein-like domain. This protein may be involved in regulating lysosome morphology. This protein may also be a target for the Hepatitis C virus and assist in viral replication. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMT5A	NM_020382.7	c.*1580C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000402868.8	NP_065115.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KMT5A	ENST00000402868.8	c.*1580C>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_020382.7	ENSP00000384629.3

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84182 AN: 151944 Hom.: 27079 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.574

GnomAD4 exome AF: 0.718 AC: 310 AN: 432 Hom.: 111 Cov.: 0 AF XY: 0.704 AC XY: 183 AN XY: 260

Gnomad4 FIN exome AF: 0.716

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.554 AC: 84176 AN: 152064 Hom.: 27072 Cov.: 32 AF XY: 0.555 AC XY: 41245 AN XY: 74332

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.571

Gnomad4 ASJ AF: 0.646

Gnomad4 EAS AF: 0.704

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.696

Gnomad4 NFE AF: 0.714

Gnomad4 OTH AF: 0.571

Alfa AF: 0.627 Hom.: 3998

Bravo AF: 0.528

Asia WGS AF: 0.584 AC: 2031 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	8.2
DANN	Benign	0.79

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: rs16917496; hg19: chr12-123893830;