9-37801071-G-T

Variant names:

• chr9-37801071-G-T
• rs775273508
• NM_024345.5:c.205G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024345.5(DCAF10):​c.205G>T​(p.Gly69*) variant causes a stop gained change involving the alteration of a non-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. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DCAF10 NM_024345.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.611
• Publications: 0 publications found

Genes affected

DCAF10 (HGNC:23686): (DDB1 and CUL4 associated factor 10) Predicted to be involved in protein ubiquitination. Part of Cul4-RING E3 ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000255872 (HGNC:):

EXOSC3 (HGNC:17944): (exosome component 3) This gene encodes a non-catalytic component of the human exosome, a complex with 3'-5' exoribonuclease activity that plays a role in numerous RNA processing and degradation activities. Related pseudogenes of this gene are found on chromosome 19 and 21. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jun 2012]

EXOSC3 Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia type 1B

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Illumina, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• pontocerebellar hypoplasia type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024345.5. 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
	DCAF10	NM_024345.5	MANE Select	c.205G>T	p.Gly69*	stop_gained	Exon 1 of 7	NP_077321.3
	DCAF10	NM_001286810.2		c.20+424G>T		intron	N/A	NP_001273739.1	A0A0A0MQT4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCAF10	ENST00000377724.8	TSL:1 MANE Select	c.205G>T	p.Gly69*	stop_gained	Exon 1 of 7	ENSP00000366953.3	Q5QP82-1
	DCAF10	ENST00000242323.8	TSL:1	c.20+424G>T		intron	N/A	ENSP00000242323.8	A0A0A0MQT4
	ENSG00000255872	ENST00000540557.1	TSL:5	n.*761-17008C>A		intron	N/A	ENSP00000457548.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1378872 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 681210

African (AFR) AF: 0.00 AC: 0 AN: 29008

American (AMR) AF: 0.00 AC: 0 AN: 36172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24510

East Asian (EAS) AF: 0.00 AC: 0 AN: 33922

South Asian (SAS) AF: 0.00 AC: 0 AN: 78202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4048

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078304

Other (OTH) AF: 0.00 AC: 0 AN: 57408

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	32
DANN	Uncertain	0.98
Eigen	Benign	-0.084
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.022	N
PhyloP100		0.61
Vest4		0.073
GERP RS		0.89
PromoterAI		-0.037	Neutral
Mutation Taster		=57/143	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs775273508; hg19: chr9-37801068;