rs6108572

Positions:

• chr20-10432111-A-T

Variant summary

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

The NM_170784.3(MKKS):​c.-649+1997T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 152,032 control chromosomes in the GnomAD database, including 21,159 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 0.52 (21159 hom., cov: 32)
• Consequence: MKKS NM_170784.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.208

Genes affected

LOC128706665 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC128706665	NM_001394148.2	c.-22+1997T>A		intron_variant		ENST00000649912.2	NP_001381077.1
LOC128706666	NM_001394149.2	c.-276+1997T>A		intron_variant		ENST00000713549.1	NP_001381078.1
MKKS	NM_170784.3	c.-649+1997T>A		intron_variant		ENST00000347364.7	NP_740754.1
MKKS	NR_072977.2	n.115+1997T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MKKS	ENST00000347364.7	c.-649+1997T>A		intron_variant		1	NM_170784.3	ENSP00000246062	P1
	ENST00000649912.2	c.-22+1997T>A		intron_variant			NM_001394148.2	ENSP00000497510	P1
	ENST00000713549.1	c.-276+1997T>A		intron_variant			NM_001394149.2	ENSP00000518845	P1

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78420 AN: 151914 Hom.: 21158 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.494

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.516 AC: 78439 AN: 152032 Hom.: 21159 Cov.: 32 AF XY: 0.517 AC XY: 38449 AN XY: 74314

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.529

Gnomad4 FIN AF: 0.647

Gnomad4 NFE AF: 0.599

Gnomad4 OTH AF: 0.488

Alfa AF: 0.561 Hom.: 3037

Bravo AF: 0.495

Asia WGS AF: 0.356 AC: 1238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6108572; hg19: chr20-10412759;