chr8-94512022-A-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_015496.5(VIRMA):c.2819T>C(p.Val940Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000326 in 1,535,336 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 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

VIRMA
NM_015496.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.64

Publications

1 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2976755).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VIRMA	NM_015496.5 link	c.2819T>C	p.Val940Ala	missense_variant	Exon 12 of 24	ENST00000297591.10	NP_056311.2	Q69YN4-1
VIRMA	NM_183009.3 link	c.2819T>C	p.Val940Ala	missense_variant	Exon 12 of 13		NP_892121.1	Q69YN4-4
VIRMA	XM_047421677.1 link	c.1814T>C	p.Val605Ala	missense_variant	Exon 13 of 25		XP_047277633.1
VIRMA	XM_047421678.1 link	c.1814T>C	p.Val605Ala	missense_variant	Exon 8 of 20		XP_047277634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
VIRMA	ENST00000297591.10 link	c.2819T>C	p.Val940Ala	missense_variant	Exon 12 of 24	1	NM_015496.5	ENSP00000297591.5	Q69YN4-1
VIRMA	ENST00000421249.2 link	c.2819T>C	p.Val940Ala	missense_variant	Exon 12 of 13	1		ENSP00000398390.2	Q69YN4-4
VIRMA	ENST00000521080.5 link	n.434T>C		non_coding_transcript_exon_variant	Exon 1 of 10	1
VIRMA	ENST00000522263.5 link	n.878T>C		non_coding_transcript_exon_variant	Exon 5 of 15	1		ENSP00000429909.1	H0YBN5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152124

Hom.:

Cov.:

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000217

AC:

AN:

1383212

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

686666

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29742

American (AMR)

AF:

0.00

AC:

AN:

37366

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24252

East Asian (EAS)

AF:

0.00

AC:

AN:

34720

South Asian (SAS)

AF:

0.00

AC:

AN:

72450

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50126

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5490

European-Non Finnish (NFE)

AF:

0.00000280

AC:

AN:

1072650

Other (OTH)

AF:

0.00

AC:

AN:

56416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000131

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41454

American (AMR)

AF:

0.00

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 07, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2819T>C (p.V940A) alteration is located in exon 12 (coding exon 12) of the KIAA1429 gene. This alteration results from a T to C substitution at nucleotide position 2819, causing the valine (V) at amino acid position 940 to be replaced by an alanine (A). 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

0.34

BayesDel_addAF

Uncertain

0.057

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.065

T;.

Eigen

Benign

0.029

Eigen_PC

Benign

0.22

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.028

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

0.90

L;L

PhyloP100

8.6

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-2.3

N;D

REVEL

Benign

0.28

Sift

Uncertain

0.0040

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.12

B;B

Vest4

0.66

MutPred

0.42

Loss of stability (P = 0.0324);Loss of stability (P = 0.0324);

MVP

0.15

MPC

0.45

ClinPred

0.91

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.49

Mutation Taster

=55/45

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over