NM_019037.3:c.5C>A

Variant names:

• chr8-144078733-C-A
• rs782335169
• NM_019037.3:c.5C>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_019037.3(EXOSC4):​c.5C>A​(p.Ala2Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EXOSC4 NM_019037.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.78

Genes affected

EXOSC4 (HGNC:18189): (exosome component 4) Enables mRNA 3'-UTR AU-rich region binding activity. Involved in nucleic acid metabolic process and positive regulation of cell growth. Acts upstream of or within defense response to virus. Located in cytosol; nucleoplasm; and transcriptionally active chromatin. Part of exosome (RNase complex). [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000290230 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a modified_residue N-acetylalanine (size 0) in uniprot entity EXOS4_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOSC4	NM_019037.3	c.5C>A	p.Ala2Glu	missense_variant	Exon 1 of 3	ENST00000316052.6	NP_061910.1
EXOSC4	XM_011517134.4	c.-123-1210C>A		intron_variant	Intron 1 of 2		XP_011515436.1
LOC124902038	XR_007061141.1	n.3096G>T		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOSC4	ENST00000316052.6	c.5C>A	p.Ala2Glu	missense_variant	Exon 1 of 3	1	NM_019037.3	ENSP00000315476.4
ENSG00000290230	ENST00000703646.1	n.5C>A		non_coding_transcript_exon_variant	Exon 1 of 8			ENSP00000515414.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1302908 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 636550

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.062	T;T
Eigen	Benign	-0.068
Eigen_PC	Benign	0.028
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.84	T;T
M_CAP	Uncertain	0.27	D
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.9	N;N
REVEL	Uncertain	0.38
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.019	D;D
Polyphen		0.65	P;.
Vest4		0.76
MutPred		0.25		Gain of disorder (P = 0.0725);Gain of disorder (P = 0.0725);
MVP		0.72
MPC		0.75
ClinPred		0.96	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.34
gMVP		0.50

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

Other links and lift over

dbSNP: rs782335169; hg19: chr8-145133636;