rs766086654

Variant names:

• chr22-29825689-C-G
• rs766086654
• NM_032204.5:c.173G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-29825689-C-G
• chr22-29825689-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032204.5(ASCC2):​c.173G>C​(p.Arg58Pro) variant causes a missense change. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R58H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ASCC2 NM_032204.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.27
• Publications: 7 publications found

Genes affected

ASCC2 (HGNC:24103): (activating signal cointegrator 1 complex subunit 2) Predicted to enable ubiquitin binding activity. Involved in regulation of transcription, DNA-templated; rescue of stalled ribosome; and ribosome-associated ubiquitin-dependent protein catabolic process. Located in nucleus. Part of activating signal cointegrator 1 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40842965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASCC2	NM_032204.5	c.173G>C	p.Arg58Pro	missense_variant	Exon 3 of 20	ENST00000307790.8	NP_115580.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASCC2	ENST00000307790.8	c.173G>C	p.Arg58Pro	missense_variant	Exon 3 of 20	1	NM_032204.5	ENSP00000305502.3

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	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	T;T;T
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	.;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.41	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.9	L;L;.
PhyloP100		4.3
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.6	D;D;D
REVEL	Benign	0.21
Sift	Benign	0.058	T;T;T
Sift4G	Benign	0.16	T;T;D
Polyphen		1.0	D;D;.
Vest4		0.83
MutPred		0.47		Gain of loop (P = 0.002);Gain of loop (P = 0.002);Gain of loop (P = 0.002);
MVP		0.44
MPC		1.2
ClinPred		0.95	D
GERP RS		6.0
Varity_R		0.91
gMVP		0.82
Mutation Taster		=61/39	polymorphism

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: rs766086654; hg19: chr22-30221678;