chr8-94509831-T-G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_015496.5(VIRMA):c.3736A>C(p.Ile1246Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000923 in 1,614,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00010 ( 0 hom. )
Consequence
VIRMA
NM_015496.5 missense
NM_015496.5 missense
Scores
2
17
Clinical Significance
Conservation
PhyloP100: 4.05
Genes affected
VIRMA (HGNC:24500): (vir like m6A methyltransferase associated) Enables RNA binding activity. Involved in mRNA alternative polyadenylation and mRNA methylation. Located in cytosol and nuclear speck. Colocalizes with RNA N6-methyladenosine methyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, VIRMA
BP4
?
Computational evidence support a benign effect (MetaRNN=0.08708003).
BS2
?
High AC in GnomAdExome at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VIRMA | NM_015496.5 | c.3736A>C | p.Ile1246Leu | missense_variant | 15/24 | ENST00000297591.10 | |
VIRMA | XM_047421677.1 | c.2731A>C | p.Ile911Leu | missense_variant | 16/25 | ||
VIRMA | XM_047421678.1 | c.2731A>C | p.Ile911Leu | missense_variant | 11/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VIRMA | ENST00000297591.10 | c.3736A>C | p.Ile1246Leu | missense_variant | 15/24 | 1 | NM_015496.5 | P1 | |
VIRMA | ENST00000521080.5 | n.1351A>C | non_coding_transcript_exon_variant | 4/10 | 1 | ||||
VIRMA | ENST00000522263.5 | c.1795A>C | p.Ile599Leu | missense_variant, NMD_transcript_variant | 8/15 | 1 | |||
VIRMA | ENST00000523405.1 | n.488A>C | non_coding_transcript_exon_variant | 2/2 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152214Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
2
AN:
152214
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250874Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135572
GnomAD3 exomes
AF:
AC:
5
AN:
250874
Hom.:
AF XY:
AC XY:
4
AN XY:
135572
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000101 AC: 147AN: 1461736Hom.: 0 Cov.: 32 AF XY: 0.000105 AC XY: 76AN XY: 727174
GnomAD4 exome
AF:
AC:
147
AN:
1461736
Hom.:
Cov.:
32
AF XY:
AC XY:
76
AN XY:
727174
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152332Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74494
GnomAD4 genome
?
AF:
AC:
2
AN:
152332
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
74494
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
0
ALSPAC
AF:
AC:
1
ExAC
?
AF:
AC:
2
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 20, 2023 | The c.3736A>C (p.I1246L) alteration is located in exon 15 (coding exon 15) of the KIAA1429 gene. This alteration results from a A to C substitution at nucleotide position 3736, causing the isoleucine (I) at amino acid position 1246 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of catalytic residue at I1246 (P = 0.0467);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at