8-144080595-G-T

Variant names:

• chr8-144080595-G-T
• rs113319063
• NM_019037.3:c.732G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_019037.3(EXOSC4):​c.732G>T​(p.Gly244Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G244G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EXOSC4 NM_019037.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 2 publications found

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]

EXOSC4 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000290230 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=1.24 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019037.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOSC4	NM_019037.3	MANE Select	c.732G>T	p.Gly244Gly	synonymous	Exon 3 of 3	NP_061910.1	Q9NPD3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOSC4	ENST00000316052.6	TSL:1 MANE Select	c.732G>T	p.Gly244Gly	synonymous	Exon 3 of 3	ENSP00000315476.4	Q9NPD3
	ENSG00000290230	ENST00000703646.1		n.705+27G>T		intron	N/A	ENSP00000515414.1	A0A994J4D9
	EXOSC4	ENST00000917256.1		c.882G>T	p.Gly294Gly	synonymous	Exon 3 of 3	ENSP00000587315.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	6.3
DANN	Benign	0.74
PhyloP100		1.2

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

Other links and lift over

dbSNP: rs113319063; hg19: chr8-145135498;