ENST00000393119:c.*351delG

Variant names:

• chr17-58205727-AC-A
• rs35298266
• NM_017777.4:c.*351delG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000393119.7(MKS1):​c.*351delG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.051 in 1,352,134 control chromosomes in the GnomAD database, including 2,171 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.039 (190 hom., cov: 31)
  • Exomes 𝑓: 0.053 (1981 hom.)
• Consequence: MKS1 ENST00000393119.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.160
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 17-58205727-AC-A is Benign according to our data. Variant chr17-58205727-AC-A is described in ClinVar as Benign. ClinVar VariationId is 1277626.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000393119.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKS1	NM_017777.4	MANE Select	c.*351delG		3_prime_UTR	Exon 18 of 18	NP_060247.2	Q9NXB0-1
	MKS1	NM_001321269.2		c.*262delG		3_prime_UTR	Exon 17 of 17	NP_001308198.1	A0A7I2V2M0
	MKS1	NM_001330397.2		c.*443delG		3_prime_UTR	Exon 16 of 16	NP_001317326.1	H0Y2S2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKS1	ENST00000393119.7	TSL:1 MANE Select	c.*351delG		3_prime_UTR	Exon 18 of 18	ENSP00000376827.2	Q9NXB0-1
	MKS1	ENST00000966002.1		c.*351delG		3_prime_UTR	Exon 18 of 18	ENSP00000636061.1
	MKS1	ENST00000678463.1		c.*262delG		3_prime_UTR	Exon 17 of 17	ENSP00000502984.1	A0A7I2V2M0

Frequencies

GnomAD3 genomes AF: 0.0389 AC: 5925 AN: 152148 Hom.: 190 Cov.: 31

Gnomad AFR AF: 0.00929

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.0264

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00828

Gnomad FIN AF: 0.0625

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0619

Gnomad OTH AF: 0.0393

GnomAD2 exomes AF: 0.0365 AC: 5531 AN: 151520 AF XY: 0.0349

Gnomad AFR exome AF: 0.00753

Gnomad AMR exome AF: 0.0228

Gnomad ASJ exome AF: 0.0141

Gnomad EAS exome AF: 0.0000927

Gnomad FIN exome AF: 0.0630

Gnomad NFE exome AF: 0.0598

Gnomad OTH exome AF: 0.0370

GnomAD4 exome AF: 0.0525 AC: 63008 AN: 1199868 Hom.: 1981 Cov.: 30 AF XY: 0.0506 AC XY: 29805 AN XY: 588612

African (AFR) AF: 0.00686 AC: 180 AN: 26244

American (AMR) AF: 0.0223 AC: 659 AN: 29534

Ashkenazi Jewish (ASJ) AF: 0.0158 AC: 285 AN: 18078

East Asian (EAS) AF: 0.000239 AC: 4 AN: 16770

South Asian (SAS) AF: 0.00754 AC: 578 AN: 76612

European-Finnish (FIN) AF: 0.0633 AC: 1875 AN: 29618

Middle Eastern (MID) AF: 0.00657 AC: 31 AN: 4718

European-Non Finnish (NFE) AF: 0.0605 AC: 57647 AN: 953146

Other (OTH) AF: 0.0387 AC: 1749 AN: 45148

GnomAD4 genome AF: 0.0389 AC: 5925 AN: 152266 Hom.: 190 Cov.: 31 AF XY: 0.0379 AC XY: 2820 AN XY: 74450

African (AFR) AF: 0.00927 AC: 385 AN: 41552

American (AMR) AF: 0.0263 AC: 403 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 59 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00829 AC: 40 AN: 4828

European-Finnish (FIN) AF: 0.0625 AC: 664 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0619 AC: 4207 AN: 68002

Other (OTH) AF: 0.0389 AC: 82 AN: 2110

Alfa AF: 0.0323 Hom.: 28

Bravo AF: 0.0347

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.16
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs35298266; hg19: chr17-56283088;