rs16996729

Positions:

• chr20-10434132-C-CCAGGCCGCCA
• chr20-10434132-C-CCAGGCCGCCACAGGCCGCCA

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_170784.3(MKKS):​c.-683_-674dupTGGCGGCCTG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0609 in 152,674 control chromosomes in the GnomAD database, including 325 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.061 (325 hom., cov: 32)
  • Exomes 𝑓: 0.030 (0 hom.)
• Consequence: MKKS NM_170784.3 5_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• 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 Benign. Variant got -9 ACMG points.

• BP6: Variant 20-10434132-C-CCAGGCCGCCA is Benign according to our data. Variant chr20-10434132-C-CCAGGCCGCCA is described in ClinVar as [Benign]. Clinvar id is 21667.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MKKS	NM_170784.3	c.-683_-674dupTGGCGGCCTG		5_prime_UTR_variant	1/6	ENST00000347364.7	NP_740754.1
LOC128706665	NM_001394148.2	c.-56_-47dupTGGCGGCCTG		5_prime_UTR_variant	1/3		NP_001381077.1
LOC128706666	NM_001394149.2	c.-310_-301dupTGGCGGCCTG		5_prime_UTR_variant	1/3		NP_001381078.1
MKKS	NR_072977.2	n.81_90dupTGGCGGCCTG		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MKKS	ENST00000347364.7	c.-683_-674dupTGGCGGCCTG		5_prime_UTR_variant	1/6	1	NM_170784.3	ENSP00000246062.4
MKKS	ENST00000651692.1	c.-770_-761dupTGGCGGCCTG		5_prime_UTR_variant	1/7			ENSP00000498849.1
MKKS	ENST00000652676.1	n.57_66dupTGGCGGCCTG		non_coding_transcript_exon_variant	1/7

Frequencies

GnomAD3 genomes AF: 0.0610 AC: 9281 AN: 152050 Hom.: 325 Cov.: 32

Gnomad AFR AF: 0.0534

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0842

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.0659

Gnomad SAS AF: 0.0499

Gnomad FIN AF: 0.0713

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0620

Gnomad OTH AF: 0.0531

GnomAD4 exome AF: 0.0296 AC: 15 AN: 506 Hom.: 0 Cov.: 0 AF XY: 0.0250 AC XY: 10 AN XY: 400

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0333

Gnomad4 NFE exome AF: 0.0317

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0610 AC: 9288 AN: 152168 Hom.: 325 Cov.: 32 AF XY: 0.0624 AC XY: 4641 AN XY: 74374

Gnomad4 AFR AF: 0.0533

Gnomad4 AMR AF: 0.0840

Gnomad4 ASJ AF: 0.0268

Gnomad4 EAS AF: 0.0661

Gnomad4 SAS AF: 0.0502

Gnomad4 FIN AF: 0.0713

Gnomad4 NFE AF: 0.0620

Gnomad4 OTH AF: 0.0535

Alfa AF: 0.0208 Hom.: 6

Asia WGS AF: 0.0580 AC: 200 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Bardet-Biedl syndrome Benign:1

Benign, no assertion criteria provided

curation

GeneReviews

Oct 13, 2009

- -

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;