Genetic Variant VPS50:c.422+36A>T (chr7-93257500-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_017667.4(VPS50):c.422+36A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

VPS50
NM_017667.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.399

Publications

12 publications found

Variant links:

Genes affected

VPS50 (HGNC:25956): (VPS50 subunit of EARP/GARPII complex) Enables SNARE binding activity. Acts upstream of or within endocytic recycling. Located in recycling endosome. Part of EARP complex. [provided by Alliance of Genome Resources, Apr 2022]

VPS50 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

VPS50 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_017667.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017667.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VPS50	NM_017667.4	MANE Select	c.422+36A>T	intron	N/A	NP_060137.2
VPS50	NM_001257998.2		c.332+36A>T	intron	N/A	NP_001244927.1	Q96JG6-3
VPS50	NM_024553.3		c.422+36A>T	intron	N/A	NP_078829.1	Q96JG6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VPS50	ENST00000305866.10	TSL:1 MANE Select	c.422+36A>T	intron	N/A	ENSP00000307666.5	Q96JG6-1
VPS50	ENST00000251739.9	TSL:1	c.422+36A>T	intron	N/A	ENSP00000251739.5	Q96JG6-2
VPS50	ENST00000441602.5	TSL:1	n.*195+36A>T	intron	N/A	ENSP00000415809.1	F2Z3F0

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151686

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1028914

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

529746

African (AFR)

AF:

0.00

AC:

AN:

23340

American (AMR)

AF:

0.00

AC:

AN:

34006

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21708

East Asian (EAS)

AF:

0.00

AC:

AN:

36616

South Asian (SAS)

AF:

0.00

AC:

AN:

70068

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51540

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4808

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

741262

Other (OTH)

AF:

0.00

AC:

AN:

45566

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

151686

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74044

African (AFR)

AF:

0.00

AC:

AN:

41370

American (AMR)

AF:

0.00

AC:

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67802

Other (OTH)

AF:

0.00

AC:

AN:

2088

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.4

(source)

DANN

Benign

0.72

PhyloP100

-0.40

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over