rs145830532

Variant names:

• chr8-144080339-C-G
• rs145830532
• NM_019037.3:c.476C>G

Your query was ambiguous. Multiple possible variants found:

• chr8-144080339-C-G
• chr8-144080339-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_019037.3(EXOSC4):​c.476C>G​(p.Ala159Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EXOSC4 NM_019037.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.23

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.772

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOSC4	NM_019037.3	c.476C>G	p.Ala159Gly	missense_variant	Exon 3 of 3	ENST00000316052.6	NP_061910.1
EXOSC4	XM_011517134.4	c.182C>G	p.Ala61Gly	missense_variant	Exon 3 of 3		XP_011515436.1
LOC124902038	XR_007061141.1	n.1490G>C		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.476C>G	p.Ala159Gly	missense_variant	Exon 3 of 3	1	NM_019037.3	ENSP00000315476.4
ENSG00000290230	ENST00000703646.1	n.476C>G		non_coding_transcript_exon_variant	Exon 3 of 8			ENSP00000515414.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	28
DANN	Benign	0.97
DEOGEN2	Benign	0.20	T;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.77	D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	2.0	M;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Benign	0.27
Sift	Benign	0.17	T;T
Sift4G	Benign	0.17	T;T
Polyphen		0.70	P;.
Vest4		0.74
MutPred		0.78		Gain of catalytic residue at C158 (P = 0.3397);.;
MVP		0.58
MPC		0.93
ClinPred		0.95	D
GERP RS		5.4
Varity_R		0.69
gMVP		0.65

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: rs145830532; hg19: chr8-145135242;