8-94509764-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2

The NM_015496.5(VIRMA):c.3803G>A(p.Arg1268Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,744 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 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

VIRMA
NM_015496.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.71

Variant links:

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]

VIRMA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PP2

Missense variant where missense usually causes diseases, VIRMA

BP4

Computational evidence support a benign effect (MetaRNN=0.31331256).

BS2

High AC in GnomAd at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
VIRMA	NM_015496.5 linkuse as main transcript	c.3803G>A	p.Arg1268Gln	missense_variant	15/24	ENST00000297591.10
VIRMA	XM_047421677.1 linkuse as main transcript	c.2798G>A	p.Arg933Gln	missense_variant	16/25
VIRMA	XM_047421678.1 linkuse as main transcript	c.2798G>A	p.Arg933Gln	missense_variant	11/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VIRMA	ENST00000297591.10 linkuse as main transcript	c.3803G>A	p.Arg1268Gln	missense_variant	15/24	1	NM_015496.5	P1	Q69YN4-1
VIRMA	ENST00000521080.5 linkuse as main transcript	n.1418G>A		non_coding_transcript_exon_variant	4/10	1
VIRMA	ENST00000522263.5 linkuse as main transcript	c.1862G>A	p.Arg621Gln	missense_variant, NMD_transcript_variant	8/15	1
VIRMA	ENST00000523405.1 linkuse as main transcript	n.555G>A		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251000

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135626

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461642

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152102

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000479

Bravo

AF:

0.0000151

ExAC

AF:

0.0000247

AC:

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 17, 2023

The c.3803G>A (p.R1268Q) alteration is located in exon 15 (coding exon 15) of the KIAA1429 gene. This alteration results from a G to A substitution at nucleotide position 3803, causing the arginine (R) at amino acid position 1268 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.42

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.026

Eigen

Benign

-0.074

Eigen_PC

Benign

0.068

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.010

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.1

MutationTaster

Benign

0.54

D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.25

REVEL

Benign

0.056

Sift

Benign

0.36

Sift4G

Benign

0.11

Polyphen

0.76

Vest4

0.49

MutPred

0.36

Gain of disorder (P = 0.2456);

MVP

0.23

MPC

0.33

ClinPred

0.087

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.050

gMVP

0.26

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over