Variant 8-94494948-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS2

The NM_015496.5(VIRMA):c.4553A>T(p.Tyr1518Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000345 in 1,447,750 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: not found (cov: 31)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

VIRMA
NM_015496.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.59

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09831008).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VIRMA	NM_015496.5 linkuse as main transcript	c.4553A>T	p.Tyr1518Phe	missense_variant	20/24	ENST00000297591.10	NP_056311.2
VIRMA	XM_047421677.1 linkuse as main transcript	c.3548A>T	p.Tyr1183Phe	missense_variant	21/25		XP_047277633.1
VIRMA	XM_047421678.1 linkuse as main transcript	c.3548A>T	p.Tyr1183Phe	missense_variant	16/20		XP_047277634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VIRMA	ENST00000297591.10 linkuse as main transcript	c.4553A>T	p.Tyr1518Phe	missense_variant	20/24	1	NM_015496.5	ENSP00000297591	P1	Q69YN4-1
VIRMA	ENST00000522263.5 linkuse as main transcript	c.*286A>T		3_prime_UTR_variant, NMD_transcript_variant	12/15	1		ENSP00000429909
VIRMA	ENST00000521080.5 linkuse as main transcript	n.5488+783A>T		intron_variant, non_coding_transcript_variant		1
VIRMA	ENST00000523263.1 linkuse as main transcript	c.270+783A>T		intron_variant, NMD_transcript_variant		3		ENSP00000428784

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

247166

Hom.:

AF XY:

0.00000749

AC XY:

AN XY:

133558

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000166

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000345

AC:

AN:

1447750

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720910

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000758

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000334

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

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

Mar 07, 2024

The c.4553A>T (p.Y1518F) alteration is located in exon 20 (coding exon 20) of the KIAA1429 gene. This alteration results from a A to T substitution at nucleotide position 4553, causing the tyrosine (Y) at amino acid position 1518 to be replaced by a phenylalanine (F). 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

0.071

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.028

Eigen

Benign

-0.18

Eigen_PC

Benign

0.042

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0053

MetaRNN

Benign

0.098

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.71

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.86

REVEL

Benign

0.070

Sift

Benign

0.50

Sift4G

Benign

0.19

Polyphen

0.079

Vest4

0.30

MutPred

0.61

Loss of catalytic residue at Y1518 (P = 0.1543);

MVP

0.093

MPC

0.26

ClinPred

0.16

GERP RS

5.2

Varity_R

0.16

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

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

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