20-10430806-A-T

Variant names:

• chr20-10430806-A-T
• rs6077785
• NM_170784.3:c.-649+3302T>A

Variant summary

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

The NM_170784.3(MKKS):​c.-649+3302T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,082 control chromosomes in the GnomAD database, including 18,997 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 0.49 (18997 hom., cov: 33)
• Consequence: MKKS NM_170784.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.432

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MKKS	NM_170784.3	c.-649+3302T>A		intron_variant	Intron 1 of 5	ENST00000347364.7	NP_740754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MKKS	ENST00000347364.7	c.-649+3302T>A		intron_variant	Intron 1 of 5	1	NM_170784.3	ENSP00000246062.4

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74725 AN: 151964 Hom.: 18995 Cov.: 33

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.492 AC: 74752 AN: 152082 Hom.: 18997 Cov.: 33 AF XY: 0.495 AC XY: 36788 AN XY: 74352

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.472

Alfa AF: 0.408 Hom.: 1192

Bravo AF: 0.477

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.63

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: rs6077785; hg19: chr20-10411454;