16-4381286-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_138440.3(VASN):c.409C>T(p.Arg137Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000459 in 1,612,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R137H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

VASN
NM_138440.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.209

Publications

3 publications found

Variant links:

Genes affected

VASN (HGNC:18517): (vasorin) Enables transforming growth factor beta binding activity. Involved in negative regulation of epithelial to mesenchymal transition and negative regulation of transforming growth factor beta receptor signaling pathway. Located in cell surface and extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

VASN links:

CORO7 (HGNC:26161): (coronin 7) This gene encodes a member of the coronin protein family. However, unlike other coronin proteins, it is not an actin-binding protein but rather functions as an F-actin regulator directing anterograde Golgi to endosome transport. The encoded protein has two tandem WD-40 domain repeats and localizes to the trans-Golgi network. The protein undergoes K33-linked polyubiquitination via an E3 ligase complex. It is thought to play an essential role in maintenance of Golgi apparatus morphology. Alternative splicing results in multiple transcripts variants; some of which form read-through transcripts with a neighboring gene. [provided by RefSeq, Dec 2016]

CORO7 links:

CORO7-PAM16 (HGNC:44424): (CORO7-PAM16 readthrough) This locus represents naturally occurring read-through transcription between the neighboring CORO7 (coronin 7) and PAM16 (presequence translocase-associated motor 16) genes on chromosome 16. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Jan 2011]

CORO7-PAM16 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.047600567).

BS2

High AC in GnomAd4 at 9 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138440.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VASN	NM_138440.3	MANE Select	c.409C>T	p.Arg137Cys	missense	Exon 2 of 2	NP_612449.2	Q6EMK4
CORO7	NM_024535.5	MANE Select	c.785+6700G>A		intron	N/A	NP_078811.3	P57737-1
CORO7-PAM16	NM_001201479.2		c.785+6700G>A		intron	N/A	NP_001188408.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VASN	ENST00000304735.4	TSL:1 MANE Select	c.409C>T	p.Arg137Cys	missense	Exon 2 of 2	ENSP00000306864.3	Q6EMK4
CORO7	ENST00000251166.9	TSL:1 MANE Select	c.785+6700G>A		intron	N/A	ENSP00000251166.4	P57737-1
CORO7-PAM16	ENST00000572467.5	TSL:2	c.785+6700G>A		intron	N/A	ENSP00000460885.1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000649

AC:

AN:

246594

AF XY:

0.0000446

show subpopulations

Gnomad AFR exome

AF:

0.0000644

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000766

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000445

AC:

AN:

1460040

Hom.:

Cov.:

115

AF XY:

0.0000344

AC XY:

AN XY:

726320

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33468

American (AMR)

AF:

0.0000448

AC:

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.000656

AC:

AN:

39664

South Asian (SAS)

AF:

0.00

AC:

AN:

86192

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52068

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000126

AC:

AN:

1111764

Other (OTH)

AF:

0.000348

AC:

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000591

AC:

AN:

152364

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.0000721

AC:

AN:

41590

American (AMR)

AF:

0.0000653

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000772

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.431

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000660

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000744

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.22

M_CAP

Benign

0.039

MetaRNN

Benign

0.048

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.2

PhyloP100

0.21

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.14

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.0050

Polyphen

0.022

Vest4

0.11

MVP

0.65

MPC

0.099

ClinPred

0.14

GERP RS

4.8

Varity_R

0.35

gMVP

0.45

Mutation Taster

=81/19

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over