rs6133922

Positions:

• chr20-10420425-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_170784.3(MKKS):​c.-418+103T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0666 in 152,268 control chromosomes in the GnomAD database, including 370 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 0.067 (370 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MKKS NM_170784.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MKKS	NM_170784.3	c.-418+103T>C		intron_variant		ENST00000347364.7	NP_740754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MKKS	ENST00000347364.7	c.-418+103T>C		intron_variant		1	NM_170784.3	ENSP00000246062.4

Frequencies

GnomAD3 genomes AF: 0.0667 AC: 10147 AN: 152150 Hom.: 370 Cov.: 32

Gnomad AFR AF: 0.0707

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0593

Gnomad ASJ AF: 0.0782

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0440

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0570

Gnomad OTH AF: 0.0703

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0666 AC: 10145 AN: 152268 Hom.: 370 Cov.: 32 AF XY: 0.0686 AC XY: 5111 AN XY: 74458

Gnomad4 AFR AF: 0.0706

Gnomad4 AMR AF: 0.0592

Gnomad4 ASJ AF: 0.0782

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.0440

Gnomad4 NFE AF: 0.0570

Gnomad4 OTH AF: 0.0691

Alfa AF: 0.0604 Hom.: 441

Bravo AF: 0.0657

Asia WGS AF: 0.119 AC: 414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.8
DANN	Benign	0.78

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: rs6133922; hg19: chr20-10401073;