NM_181503.3:c.815G>A

Variant names:

• chr13-37009283-G-A
• NM_181503.3:c.815G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181503.3(EXOSC8):​c.815G>A​(p.Ser272Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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: EXOSC8 NM_181503.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.02

Genes affected

EXOSC8 (HGNC:17035): (exosome component 8) This gene encodes a 3'-5' exoribonuclease that specifically interacts with mRNAs containing AU-rich elements. The encoded protein is part of the exosome complex that is important for the degradation of numerous RNA species. A pseudogene of this gene is found on chromosome 6. [provided by RefSeq, Mar 2009]

SUPT20H (HGNC:20596): (SPT20 homolog, SAGA complex component) Predicted to enable transcription coregulator activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within positive regulation of gluconeogenesis and positive regulation of transcription by RNA polymerase II. Part of SAGA-type complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25849658).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOSC8	NM_181503.3	c.815G>A	p.Ser272Asn	missense_variant	Exon 11 of 11	ENST00000389704.4	NP_852480.1
SUPT20H	NM_001014286.3	c.*389C>T		downstream_gene_variant		ENST00000350612.11	NP_001014308.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOSC8	ENST00000389704.4	c.815G>A	p.Ser272Asn	missense_variant	Exon 11 of 11	1	NM_181503.3	ENSP00000374354.3
SUPT20H	ENST00000350612.11	c.*389C>T		downstream_gene_variant		1	NM_001014286.3	ENSP00000218894.10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443620 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 719168

Gnomad4 AFR exome AF: 0.0000302

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.035	T;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.77	T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	2.0	M;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.65	N;N
REVEL	Uncertain	0.36
Sift	Benign	0.13	T;D
Sift4G	Benign	0.17	T;D
Polyphen		0.034	B;.
Vest4		0.59
MutPred		0.27		Loss of phosphorylation at S272 (P = 0.0175);.;
MVP		0.52
MPC		0.15
ClinPred		0.68	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.28

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: chr13-37583420;