8-94494912-G-A

Position:

• chr8-94494912-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015496.5(VIRMA):​c.4589C>T​(p.Ser1530Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: VIRMA NM_015496.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.26

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VIRMA	NM_015496.5	c.4589C>T	p.Ser1530Phe	missense_variant	20/24	ENST00000297591.10	NP_056311.2
VIRMA	XM_047421677.1	c.3584C>T	p.Ser1195Phe	missense_variant	21/25		XP_047277633.1
VIRMA	XM_047421678.1	c.3584C>T	p.Ser1195Phe	missense_variant	16/20		XP_047277634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VIRMA	ENST00000297591.10	c.4589C>T	p.Ser1530Phe	missense_variant	20/24	1	NM_015496.5	ENSP00000297591	P1
VIRMA	ENST00000522263.5	c.*322C>T		3_prime_UTR_variant, NMD_transcript_variant	12/15	1		ENSP00000429909
VIRMA	ENST00000521080.5	n.5488+819C>T		intron_variant, non_coding_transcript_variant		1
VIRMA	ENST00000523263.1	c.270+819C>T		intron_variant, NMD_transcript_variant		3		ENSP00000428784

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 23, 2024

The c.4589C>T (p.S1530F) alteration is located in exon 20 (coding exon 20) of the KIAA1429 gene. This alteration results from a C to T substitution at nucleotide position 4589, causing the serine (S) at amino acid position 1530 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	Uncertain	0.34
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.075	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.36
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.62
MutPred		0.41		Gain of methylation at K1529 (P = 0.0287);
MVP		0.14
MPC		0.81
ClinPred		0.95	D
GERP RS		5.2
Varity_R		0.48
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-95507140;