rs145828514

Variant names:

• chr8-144080481-C-A
• NM_019037.3:c.618C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-144080481-C-A
• chr8-144080481-C-G
• chr8-144080481-C-T

Variant summary

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

The NM_019037.3(EXOSC4):​c.618C>A​(p.His206Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,384 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: EXOSC4 NM_019037.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780

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 2 ACMG points.

• 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.618C>A	p.His206Gln	missense_variant	Exon 3 of 3	ENST00000316052.6	NP_061910.1
EXOSC4	XM_011517134.4	c.324C>A	p.His108Gln	missense_variant	Exon 3 of 3		XP_011515436.1
LOC124902038	XR_007061141.1	n.1348G>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.618C>A	p.His206Gln	missense_variant	Exon 3 of 3	1	NM_019037.3	ENSP00000315476.4
ENSG00000290230	ENST00000703646.1	n.618C>A		non_coding_transcript_exon_variant	Exon 3 of 8			ENSP00000515414.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455384 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724358

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T;.
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-6.3	D;D
REVEL	Uncertain	0.36
Sift	Benign	0.098	T;T
Sift4G	Benign	0.083	T;D
Polyphen		0.99	D;.
Vest4		0.63
MutPred		0.55		Loss of catalytic residue at R204 (P = 0.0824);.;
MVP		0.31
MPC		0.85
ClinPred		0.99	D
GERP RS		-5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.73
gMVP		0.51

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-145135384;