Genetic Variant VIRMA:p.Arg1571His (chr8-94492748-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_015496.5(VIRMA):c.4712G>A(p.Arg1571His) variant causes a missense change. The variant allele was found at a frequency of 0.000117 in 1,613,660 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

VIRMA
NM_015496.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.70

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 -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.32033655).

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VIRMA	NM_015496.5 link	c.4712G>A	p.Arg1571His	missense_variant	Exon 21 of 24	ENST00000297591.10	NP_056311.2	Q69YN4-1
VIRMA	XM_047421677.1 link	c.3707G>A	p.Arg1236His	missense_variant	Exon 22 of 25		XP_047277633.1
VIRMA	XM_047421678.1 link	c.3707G>A	p.Arg1236His	missense_variant	Exon 17 of 20		XP_047277634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VIRMA	ENST00000297591.10 link	c.4712G>A	p.Arg1571His	missense_variant	Exon 21 of 24	1	NM_015496.5	ENSP00000297591.5		Q69YN4-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251266

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000123

AC:

180

AN:

1461624

Hom.:

Cov.:

AF XY:

0.000131

AC XY:

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000154

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152036

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000354

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4712G>A (p.R1571H) alteration is located in exon 21 (coding exon 21) of the KIAA1429 gene. This alteration results from a G to A substitution at nucleotide position 4712, causing the arginine (R) at amino acid position 1571 to be replaced by a histidine (H). 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

0.15

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.042

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.41

MutationAssessor

Benign

1.8

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-2.3

REVEL

Benign

0.24

Sift

Uncertain

0.0040

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.48

MutPred

0.37

Gain of catalytic residue at E1570 (P = 0.0683);

MVP

0.13

MPC

1.1

ClinPred

0.32

GERP RS

5.5

Varity_R

0.31

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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