rs1555599203

Positions:

• chr17-58212391-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017777.4(MKS1):​c.902C>G​(p.Thr301Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MKS1 NM_017777.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.06

Genes affected

MKS1 (HGNC:7121): (MKS transition zone complex subunit 1) The protein encoded by this gene localizes to the basal body and is required for formation of the primary cilium in ciliated epithelial cells. Mutations in this gene result in Meckel syndrome type 1 and in Bardet-Biedl syndrome type 13. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17476067).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MKS1	NM_017777.4	c.902C>G	p.Thr301Ser	missense_variant	9/18	ENST00000393119.7	NP_060247.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MKS1	ENST00000393119.7	c.902C>G	p.Thr301Ser	missense_variant	9/18	1	NM_017777.4	ENSP00000376827	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Sep 23, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Benign	0.90
DEOGEN2	Benign	0.13	T;T;.;T
Eigen	Benign	-0.22
Eigen_PC	Benign	0.086
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.74	T;T;T;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.91	N;.;.;.
MutationTaster	Benign	0.78	N;N;N;N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.91	N;.;N;.
REVEL	Benign	0.14
Sift	Benign	0.71	T;.;T;.
Sift4G	Benign	0.70	T;T;T;T
Polyphen		0.0010	B;.;.;.
Vest4		0.23
MutPred		0.26		Gain of disorder (P = 0.0807);Gain of disorder (P = 0.0807);.;.;
MVP		0.78
MPC		0.23
ClinPred		0.54	D
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.066
gMVP		0.13

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: rs1555599203; hg19: chr17-56289752;