rs142958086

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001193315.2(VIPAS39):c.836+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00849 in 1,612,554 control chromosomes in the GnomAD database, including 160 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 19 hom., cov: 32)

Exomes 𝑓: 0.0085 ( 141 hom. )

Consequence

VIPAS39
NM_001193315.2 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.577

Publications

4 publications found

Variant links:

Genes affected

VIPAS39 (HGNC:20347): (VPS33B interacting protein, apical-basolateral polarity regulator, spe-39 homolog) Involved in endosome to lysosome transport and intracellular protein transport. Acts upstream of or within collagen metabolic process and peptidyl-lysine hydroxylation. Located in Golgi apparatus and endosome. Implicated in arthrogryposis, renal dysfunction, and cholestasis 2. [provided by Alliance of Genome Resources, Apr 2022]

VIPAS39 Gene-Disease associations (from GenCC):

arthrogryposis, renal dysfunction, and cholestasis 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
arthrogryposis-renal dysfunction-cholestasis syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

VIPAS39 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=-0.81).

BP6

Variant 14-77437793-T-C is Benign according to our data. Variant chr14-77437793-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 261492.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00876 (1334/152308) while in subpopulation SAS AF = 0.0367 (177/4826). AF 95% confidence interval is 0.0323. There are 19 homozygotes in GnomAd4. There are 631 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VIPAS39	NM_001193315.2 link	c.836+15A>G		intron_variant	Intron 12 of 19	ENST00000557658.6	NP_001180244.1	Q9H9C1-1Q6IA61

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VIPAS39	ENST00000557658.6 link	c.836+15A>G		intron_variant	Intron 12 of 19	1	NM_001193315.2	ENSP00000452191.1		Q9H9C1-1

Frequencies

GnomAD3 genomes

AF:

0.00875

AC:

1331

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00731

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00622

Gnomad ASJ

AF:

0.0409

Gnomad EAS

AF:

0.0148

Gnomad SAS

AF:

0.0371

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00723

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.0114

AC:

2867

AN:

251378

AF XY:

0.0132

show subpopulations

Gnomad AFR exome

AF:

0.00677

Gnomad AMR exome

AF:

0.00483

Gnomad ASJ exome

AF:

0.0352

Gnomad EAS exome

AF:

0.0107

Gnomad FIN exome

AF:

0.00143

Gnomad NFE exome

AF:

0.00711

Gnomad OTH exome

AF:

0.0139

GnomAD4 exome

AF:

0.00847

AC:

12362

AN:

1460246

Hom.:

141

Cov.:

AF XY:

0.00964

AC XY:

7001

AN XY:

726516

show subpopulations

African (AFR)

AF:

0.00700

AC:

234

AN:

33442

American (AMR)

AF:

0.00543

AC:

243

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0365

AC:

953

AN:

26112

East Asian (EAS)

AF:

0.0203

AC:

804

AN:

39672

South Asian (SAS)

AF:

0.0377

AC:

3250

AN:

86204

European-Finnish (FIN)

AF:

0.00159

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.0300

AC:

173

AN:

5766

European-Non Finnish (NFE)

AF:

0.00528

AC:

5862

AN:

1110578

Other (OTH)

AF:

0.0126

AC:

758

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

596

1193

1789

2386

2982

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

248

496

744

992

1240

<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:

0.00876

AC:

1334

AN:

152308

Hom.:

Cov.:

AF XY:

0.00847

AC XY:

631

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.00741

AC:

308

AN:

41562

American (AMR)

AF:

0.00621

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0409

AC:

142

AN:

3470

East Asian (EAS)

AF:

0.0148

AC:

AN:

5188

South Asian (SAS)

AF:

0.0367

AC:

177

AN:

4826

European-Finnish (FIN)

AF:

0.00104

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00723

AC:

492

AN:

68022

Other (OTH)

AF:

0.0104

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

122

182

243

304

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0113

Hom.:

Bravo

AF:

0.00800

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 10, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.1

(source)

DANN

Benign

0.78

PhyloP100

-0.58

Mutation Taster

=100/0

polymorphism

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over