Genetic Variant VASN:p.Arg48* (chr16-4381019-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_138440.3(VASN):c.142C>T(p.Arg48*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,228 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

VASN
NM_138440.3 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.61

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.142C>T	p.Arg48*	stop_gained	Exon 2 of 2	NP_612449.2	Q6EMK4
CORO7	NM_024535.5	MANE Select	c.785+6967G>A		intron	N/A	NP_078811.3	P57737-1
CORO7-PAM16	NM_001201479.2		c.785+6967G>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.142C>T	p.Arg48*	stop_gained	Exon 2 of 2	ENSP00000306864.3	Q6EMK4
CORO7	ENST00000251166.9	TSL:1 MANE Select	c.785+6967G>A		intron	N/A	ENSP00000251166.4	P57737-1
CORO7-PAM16	ENST00000572467.5	TSL:2	c.785+6967G>A		intron	N/A	ENSP00000460885.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

238808

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457228

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724798

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33428

American (AMR)

AF:

0.00

AC:

AN:

44366

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26042

East Asian (EAS)

AF:

0.00

AC:

AN:

39576

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85764

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51272

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110840

Other (OTH)

AF:

0.00

AC:

AN:

60178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.15

PhyloP100

-1.6

Vest4

0.071

GERP RS

-5.7

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over