rs117007334

chr17-58207855-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_017777.4(MKS1):c.1273+39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,540,370 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (9 hom.)
• Consequence: MKS1 NM_017777.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.298

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-58207855-G-A is Benign according to our data. Variant chr17-58207855-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 260881.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-58207855-G-A is described in Lovd as [Benign].
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MKS1	NM_017777.4	c.1273+39C>T		intron_variant		ENST00000393119.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MKS1	ENST00000393119.7	c.1273+39C>T		intron_variant		1	NM_017777.4	P1

Frequencies

GnomAD3 genomes AF: 0.00108 AC: 165 AN: 152186 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00126

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00143 AC: 355 AN: 247722 Hom.: 2 AF XY: 0.00143 AC XY: 192 AN XY: 134450

Gnomad AFR exome AF: 0.000325

Gnomad AMR exome AF: 0.000988

Gnomad ASJ exome AF: 0.0130

Gnomad EAS exome AF: 0.0000557

Gnomad SAS exome AF: 0.000327

Gnomad FIN exome AF: 0.000141

Gnomad NFE exome AF: 0.00140

Gnomad OTH exome AF: 0.00249

GnomAD4 exome AF: 0.00117 AC: 1630 AN: 1388066 Hom.: 9 Cov.: 26 AF XY: 0.00123 AC XY: 851 AN XY: 694518

Gnomad4 AFR exome AF: 0.000282

Gnomad4 AMR exome AF: 0.000943

Gnomad4 ASJ exome AF: 0.0126

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.000378

Gnomad4 FIN exome AF: 0.000113

Gnomad4 NFE exome AF: 0.00102

Gnomad4 OTH exome AF: 0.00193

GnomAD4 genome AF: 0.00109 AC: 166 AN: 152304 Hom.: 1 Cov.: 32 AF XY: 0.000967 AC XY: 72 AN XY: 74468

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00126

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00305 Hom.: 2

Bravo AF: 0.00114

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00207

EpiControl AF: 0.00190

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	9.2
Dann	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs117007334; hg19: chr17-56285216;