20-10434132-C-CCAGGCCGCCACAGGCCGCCA

Position:

• chr20-10434132-C-CCAGGCCGCCACAGGCCGCCA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_170784.3(MKKS):​c.-674_-673insTGGCGGCCTGTGGCGGCCTG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,202 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000020 (0 hom., cov: 32)
• Consequence: MKKS NM_170784.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69

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]

LOC128706665 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MKKS	NM_170784.3	c.-674_-673insTGGCGGCCTGTGGCGGCCTG		5_prime_UTR_variant	1/6	ENST00000347364.7	NP_740754.1
LOC128706665	NM_001394148.2	c.-47_-46insTGGCGGCCTGTGGCGGCCTG		5_prime_UTR_variant	1/3		NP_001381077.1
LOC128706666	NM_001394149.2	c.-301_-300insTGGCGGCCTGTGGCGGCCTG		5_prime_UTR_variant	1/3		NP_001381078.1
MKKS	NR_072977.2	n.90_91insTGGCGGCCTGTGGCGGCCTG		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MKKS	ENST00000347364.7	c.-674_-673insTGGCGGCCTGTGGCGGCCTG		5_prime_UTR_variant	1/6	1	NM_170784.3	ENSP00000246062.4
MKKS	ENST00000651692.1	c.-761_-760insTGGCGGCCTGTGGCGGCCTG		5_prime_UTR_variant	1/7			ENSP00000498849.1
MKKS	ENST00000652676.1	n.66_67insTGGCGGCCTGTGGCGGCCTG		non_coding_transcript_exon_variant	1/7

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152084 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152202 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74390

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16996729; hg19: chr20-10414780;