19-18568345-C-T

Variant names:

• chr19-18568345-C-T
• rs1468475
• NM_024069.4:c.302-57C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024069.4(KXD1):​c.302-57C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 1,304,212 control chromosomes in the GnomAD database, including 199,405 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 0.48 (19051 hom., cov: 30)
  • Exomes 𝑓: 0.55 (180354 hom.)
• Consequence: KXD1 NM_024069.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370
• Publications: 19 publications found

Genes affected

KXD1 (HGNC:28420): (KxDL motif containing 1) Involved in lysosome localization. Part of BORC complex. [provided by Alliance of Genome Resources, Apr 2022]

UBA52 (HGNC:12458): (ubiquitin A-52 residue ribosomal protein fusion product 1) Ubiquitin is a highly conserved nuclear and cytoplasmic protein that has a major role in targeting cellular proteins for degradation by the 26S proteosome. It is also involved in the maintenance of chromatin structure, the regulation of gene expression, and the stress response. Ubiquitin is synthesized as a precursor protein consisting of either polyubiquitin chains or a single ubiquitin moiety fused to an unrelated protein. This gene encodes a fusion protein consisting of ubiquitin at the N terminus and ribosomal protein L40 at the C terminus, a C-terminal extension protein (CEP). Multiple processed pseudogenes derived from this gene are present in the genome. [provided by RefSeq, Jul 2008]

KXD1-AS1 (HGNC:56662): (KXD1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024069.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KXD1	NM_024069.4	MANE Select	c.302-57C>T		intron	N/A	NP_076974.2	Q9BQD3
	KXD1	NM_001171948.2		c.302-57C>T		intron	N/A	NP_001165419.1	Q9BQD3
	KXD1	NM_001171949.2		c.302-57C>T		intron	N/A	NP_001165420.1	Q9BQD3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KXD1	ENST00000222307.9	TSL:1 MANE Select	c.302-57C>T		intron	N/A	ENSP00000222307.3	Q9BQD3
	KXD1	ENST00000595870.5	TSL:1	c.302-57C>T		intron	N/A	ENSP00000468949.1	M0QX74
	KXD1	ENST00000916838.1		c.386-57C>T		intron	N/A	ENSP00000586897.1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72634 AN: 151582 Hom.: 19032 Cov.: 30

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.494

GnomAD4 exome AF: 0.554 AC: 638555 AN: 1152512 Hom.: 180354 AF XY: 0.551 AC XY: 321823 AN XY: 583990

African (AFR) AF: 0.237 AC: 6513 AN: 27458

American (AMR) AF: 0.599 AC: 25522 AN: 42584

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 10130 AN: 22048

East Asian (EAS) AF: 0.661 AC: 25201 AN: 38116

South Asian (SAS) AF: 0.475 AC: 35985 AN: 75728

European-Finnish (FIN) AF: 0.616 AC: 31686 AN: 51418

Middle Eastern (MID) AF: 0.419 AC: 2142 AN: 5110

European-Non Finnish (NFE) AF: 0.565 AC: 474517 AN: 840096

Other (OTH) AF: 0.538 AC: 26859 AN: 49954

GnomAD4 genome AF: 0.479 AC: 72686 AN: 151700 Hom.: 19051 Cov.: 30 AF XY: 0.484 AC XY: 35897 AN XY: 74102

African (AFR) AF: 0.251 AC: 10384 AN: 41362

American (AMR) AF: 0.542 AC: 8257 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1503 AN: 3470

East Asian (EAS) AF: 0.656 AC: 3372 AN: 5140

South Asian (SAS) AF: 0.476 AC: 2285 AN: 4804

European-Finnish (FIN) AF: 0.618 AC: 6489 AN: 10496

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38667 AN: 67886

Other (OTH) AF: 0.498 AC: 1045 AN: 2100

Alfa AF: 0.516 Hom.: 13765

Bravo AF: 0.466

Asia WGS AF: 0.579 AC: 2014 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.42
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1468475; hg19: chr19-18679155; COSMIC: COSV55888995; COSMIC: COSV55888995;