NM_032357.4:c.216-9G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_032357.4(VMA22):​c.216-9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000503 in 1,610,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

VMA22
NM_032357.4 intron

Scores

2
Splicing: ADA: 0.00008206
2

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.340
Variant links:
Genes affected
VMA22 (HGNC:28178): (coiled-coil domain containing 115) The protein encoded by this gene has been observed to localize to the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC) and coat protein complex I (COPI) vesicles in some human cells. The encoded protein shares some homology with the yeast V-ATPase assembly factor Vma22p, and the orthologous protein in mouse promotes cell proliferation and suppresses cell death. Defects in this gene are a cause of congenital disorder of glycosylation, type IIo in humans. [provided by RefSeq, Mar 2016]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 2-130341758-C-T is Benign according to our data. Variant chr2-130341758-C-T is described in ClinVar as [Benign]. Clinvar id is 1559277.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VMA22NM_032357.4 linkc.216-9G>A intron_variant Intron 2 of 4 ENST00000259229.7 NP_115733.2 Q96NT0-1A1QKJ6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCDC115ENST00000259229.7 linkc.216-9G>A intron_variant Intron 2 of 4 1 NM_032357.4 ENSP00000259229.2 Q96NT0-1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152158
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00135
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000194
AC:
48
AN:
246940
AF XY:
0.000208
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00225
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000901
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000507
AC:
74
AN:
1458302
Hom.:
0
Cov.:
31
AF XY:
0.0000662
AC XY:
48
AN XY:
725458
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33400
American (AMR)
AF:
0.00
AC:
0
AN:
44612
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26096
East Asian (EAS)
AF:
0.000832
AC:
33
AN:
39686
South Asian (SAS)
AF:
0.000209
AC:
18
AN:
85992
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52604
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4148
European-Non Finnish (NFE)
AF:
0.00000180
AC:
2
AN:
1111600
Other (OTH)
AF:
0.000349
AC:
21
AN:
60164
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.467
Heterozygous variant carriers
0
4
9
13
18
22
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
4
8
12
16
20
<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:
0.0000460
AC:
7
AN:
152276
Hom.:
0
Cov.:
33
AF XY:
0.0000537
AC XY:
4
AN XY:
74448
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41562
American (AMR)
AF:
0.00
AC:
0
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00116
AC:
6
AN:
5172
South Asian (SAS)
AF:
0.000207
AC:
1
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10618
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68010
Other (OTH)
AF:
0.00
AC:
0
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00
Hom.:
0
Bravo
AF:
0.0000718
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jul 26, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

CCDC115-related disorder Benign:1
Sep 26, 2019
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
CADD
Benign
12
DANN
Benign
0.87
PhyloP100
-0.34
PromoterAI
-0.11
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000082
dbscSNV1_RF
Benign
0.0080
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs536399900; hg19: chr2-131099331; COSMIC: COSV52092267; COSMIC: COSV52092267; API