rs73329636

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017777.4(MKS1):c.191-44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 1,584,240 control chromosomes in the GnomAD database, including 1,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 556 hom., cov: 32)

Exomes 𝑓: 0.030 ( 1017 hom. )

Consequence

MKS1
NM_017777.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.506

Publications

3 publications found

Variant links:

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]

MKS1 Gene-Disease associations (from GenCC):

ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Meckel syndrome, type 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Myriad Women’s Health
Bardet-Biedl syndrome 13
Inheritance: Unknown, AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
Joubert syndrome 28
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Bardet-Biedl syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Joubert syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Joubert syndrome with ocular defect
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Meckel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MKS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 17-58216780-C-T is Benign according to our data. Variant chr17-58216780-C-T is described in ClinVar as Benign. ClinVar VariationId is 126273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017777.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MKS1	NM_017777.4	MANE Select	c.191-44G>A	intron	N/A	NP_060247.2	Q9NXB0-1
MKS1	NM_001321269.2		c.191-44G>A	intron	N/A	NP_001308198.1	A0A7I2V2M0
MKS1	NM_001330397.2		c.191-44G>A	intron	N/A	NP_001317326.1	H0Y2S2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MKS1	ENST00000393119.7	TSL:1 MANE Select	c.191-44G>A	intron	N/A	ENSP00000376827.2	Q9NXB0-1
MKS1	ENST00000537529.7	TSL:1	c.-239-44G>A	intron	N/A	ENSP00000442096.3	A0A0S2Z5Z2
MKS1	ENST00000966002.1		c.191-44G>A	intron	N/A	ENSP00000636061.1

Frequencies

GnomAD3 genomes

AF:

0.0631

AC:

9602

AN:

152130

Hom.:

554

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0367

Gnomad ASJ

AF:

0.0669

Gnomad EAS

AF:

0.00771

Gnomad SAS

AF:

0.0225

Gnomad FIN

AF:

0.0295

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0277

Gnomad OTH

AF:

0.0645

GnomAD2 exomes

AF:

0.0373

AC:

9230

AN:

247654

AF XY:

0.0356

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.0265

Gnomad ASJ exome

AF:

0.0723

Gnomad EAS exome

AF:

0.00625

Gnomad FIN exome

AF:

0.0277

Gnomad NFE exome

AF:

0.0295

Gnomad OTH exome

AF:

0.0461

GnomAD4 exome

AF:

0.0305

AC:

43607

AN:

1431992

Hom.:

1017

Cov.:

AF XY:

0.0302

AC XY:

21602

AN XY:

714202

show subpopulations

African (AFR)

AF:

0.159

AC:

5239

AN:

32854

American (AMR)

AF:

0.0291

AC:

1296

AN:

44550

Ashkenazi Jewish (ASJ)

AF:

0.0700

AC:

1813

AN:

25908

East Asian (EAS)

AF:

0.0128

AC:

506

AN:

39558

South Asian (SAS)

AF:

0.0291

AC:

2489

AN:

85456

European-Finnish (FIN)

AF:

0.0303

AC:

1618

AN:

53334

Middle Eastern (MID)

AF:

0.0780

AC:

446

AN:

5716

European-Non Finnish (NFE)

AF:

0.0257

AC:

27884

AN:

1085186

Other (OTH)

AF:

0.0390

AC:

2316

AN:

59430

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

2266

4532

6797

9063

11329

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1130

2260

3390

4520

5650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0631

AC:

9609

AN:

152248

Hom.:

556

Cov.:

AF XY:

0.0622

AC XY:

4634

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.152

AC:

6296

AN:

41528

American (AMR)

AF:

0.0367

AC:

561

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0669

AC:

232

AN:

3470

East Asian (EAS)

AF:

0.00772

AC:

AN:

5178

South Asian (SAS)

AF:

0.0223

AC:

108

AN:

4834

European-Finnish (FIN)

AF:

0.0295

AC:

313

AN:

10606

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0277

AC:

1885

AN:

68018

Other (OTH)

AF:

0.0639

AC:

135

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

445

891

1336

1782

2227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0464

Hom.:

Bravo

AF:

0.0685

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Bardet-Biedl syndrome 13 (1)

Joubert syndrome 28 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

0.51

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over