rs113994193

Variant names:

• chr20-10431708-T-TCAGGCCGCCA
• rs113994193
• ENST00000399054.6:c.-674_-673insTGGCGGCCTG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000399054.6(MKKS):​c.-674_-673insTGGCGGCCTG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MKKS ENST00000399054.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• Publications: 0 publications found

Genes affected

MKKS (HGNC:7108): (MKKS centrosomal shuttling protein) This gene encodes a protein which shares sequence similarity with other members of the type II chaperonin family. The encoded protein is a centrosome-shuttling protein and plays an important role in cytokinesis. This protein also interacts with other type II chaperonin members to form a complex known as the BBSome, which involves ciliary membrane biogenesis. This protein is encoded by a downstream open reading frame (dORF). Several upstream open reading frames (uORFs) have been identified, which repress the translation of the dORF, and two of which can encode small mitochondrial membrane proteins. Mutations in this gene have been observed in patients with Bardet-Biedl syndrome type 6, also known as McKusick-Kaufman syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2023]

MKKS Gene-Disease associations (from GenCC):

• McKusick-Kaufman syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• Bardet-Biedl syndrome 6

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOC128706665 (HGNC:0):

ENSG00000285508 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MKKS	NM_170784.3	c.-649+2399_-649+2400insTGGCGGCCTG		intron_variant	Intron 1 of 5	ENST00000347364.7	NP_740754.1
LOC128706665	NM_001394148.2	c.-22+2399_-22+2400insTGGCGGCCTG		intron_variant	Intron 1 of 2	ENST00000649912.2	NP_001381077.1
LOC128706666	NM_001394149.2	c.-276+2399_-276+2400insTGGCGGCCTG		intron_variant	Intron 1 of 2	ENST00000713549.1	NP_001381078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MKKS	ENST00000347364.7	c.-649+2399_-649+2400insTGGCGGCCTG		intron_variant	Intron 1 of 5	1	NM_170784.3	ENSP00000246062.4
ENSG00000285723	ENST00000649912.2	c.-22+2399_-22+2400insTGGCGGCCTG		intron_variant	Intron 1 of 2		NM_001394148.2	ENSP00000497510.1
ENSG00000285508	ENST00000713549.1	c.-276+2399_-276+2400insTGGCGGCCTG		intron_variant	Intron 1 of 2		NM_001394149.2	ENSP00000518845.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.19

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs113994193; hg19: chr20-10412356;