rs760157209

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_138440.3(VASN):​c.361C>G​(p.Arg121Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R121C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Consequence

VASN
NM_138440.3 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.13
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]
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-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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3307566).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VASNNM_138440.3 linkc.361C>G p.Arg121Gly missense_variant Exon 2 of 2 ENST00000304735.4 NP_612449.2 Q6EMK4
CORO7NM_024535.5 linkc.785+6748G>C intron_variant Intron 9 of 27 ENST00000251166.9 NP_078811.3 P57737-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VASNENST00000304735.4 linkc.361C>G p.Arg121Gly missense_variant Exon 2 of 2 1 NM_138440.3 ENSP00000306864.3 Q6EMK4
CORO7ENST00000251166.9 linkc.785+6748G>C intron_variant Intron 9 of 27 1 NM_024535.5 ENSP00000251166.4 P57737-1
CORO7-PAM16ENST00000572467.5 linkc.785+6748G>C intron_variant Intron 9 of 30 2 ENSP00000460885.1 A0A0A6YYL4

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
116
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.063
T
BayesDel_noAF
Benign
-0.33
CADD
Uncertain
24
DANN
Benign
0.92
DEOGEN2
Benign
0.061
T
Eigen
Benign
0.11
Eigen_PC
Benign
0.21
FATHMM_MKL
Uncertain
0.80
D
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.33
T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
0.88
L
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.87
N
REVEL
Benign
0.14
Sift
Benign
0.23
T
Sift4G
Benign
0.47
T
Polyphen
0.91
P
Vest4
0.40
MutPred
0.53
Loss of MoRF binding (P = 0.0047);
MVP
0.49
MPC
0.18
ClinPred
0.37
T
GERP RS
5.8
Varity_R
0.24
gMVP
0.38

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs760157209; hg19: chr16-4431239; API