rs1311306088

Variant names:

• chr17-58218682-G-A
• rs1311306088
• ENST00000537529.7:c.-302C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-58218682-G-A
• chr17-58218682-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001321268.2(MKS1):​c.-384C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000124 in 1,613,912 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MKS1 NM_001321268.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.80
• Publications: 0 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]

LPO (HGNC:6678): (lactoperoxidase) This gene encodes a member of the peroxidase family of proteins. The encoded preproprotein is proteolytically processed to generate the mature enzyme. Following its secretion from salivary, mammary, and other mucosal glands, this enzyme catalyzes the generation of the antimicrobial substance hypothiocyanous acid. This gene is present in a gene cluster on chromosome 17. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14642349).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321268.2. 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.128C>T	p.Pro43Leu	missense	Exon 2 of 18	NP_060247.2	Q9NXB0-1
	MKS1	NM_001321268.2		c.-384C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 17	NP_001308197.1
	MKS1	NM_001321269.2		c.128C>T	p.Pro43Leu	missense	Exon 2 of 17	NP_001308198.1	A0A7I2V2M0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKS1	ENST00000537529.7	TSL:1	c.-302C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 18	ENSP00000442096.3	A0A0S2Z5Z2
	MKS1	ENST00000393119.7	TSL:1 MANE Select	c.128C>T	p.Pro43Leu	missense	Exon 2 of 18	ENSP00000376827.2	Q9NXB0-1
	MKS1	ENST00000537529.7	TSL:1	c.-302C>T		5_prime_UTR	Exon 2 of 18	ENSP00000442096.3	A0A0S2Z5Z2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152122 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461790 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727188

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111948

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152122 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74298

African (AFR) AF: 0.00 AC: 0 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Benign	0.92
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.073
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.2	L
PhyloP100		4.8
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.083
Sift	Benign	0.74	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.30
MutPred		0.33		Gain of helix (P = 0.0078)
MVP		0.79
MPC		0.26
ClinPred		0.35	T
GERP RS		5.7
PromoterAI		0.0020	Neutral
Varity_R		0.11
gMVP		0.37
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1311306088; hg19: chr17-56296043;