Genetic Variant ASCC2:p.Gly561Ser (chr22-29800998-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032204.5(ASCC2):c.1681G>A(p.Gly561Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000901 in 1,443,308 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: 33)

Exomes 𝑓: 0.0000090 ( 0 hom. )

Consequence

ASCC2
NM_032204.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.16

Variant links:

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]

ASCC2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39458284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASCC2	NM_032204.5 link	c.1681G>A	p.Gly561Ser	missense_variant	Exon 15 of 20	ENST00000307790.8	NP_115580.2	Q9H1I8-1A0A024R1F9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASCC2	ENST00000307790.8 link	c.1681G>A	p.Gly561Ser	missense_variant	Exon 15 of 20	1	NM_032204.5	ENSP00000305502.3		Q9H1I8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248074

Hom.:

AF XY:

0.00000746

AC XY:

AN XY:

134086

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000295

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000901

AC:

AN:

1443308

Hom.:

Cov.:

AF XY:

0.00000979

AC XY:

AN XY:

714766

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000226

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:

0.0000109

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1681G>A (p.G561S) alteration is located in exon 15 (coding exon 14) of the ASCC2 gene. This alteration results from a G to A substitution at nucleotide position 1681, causing the glycine (G) at amino acid position 561 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

T;.;T;T

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.79

.;T;T;T

M_CAP

Benign

0.057

MetaRNN

Benign

0.39

T;T;T;T

MetaSVM

Benign

-0.36

MutationAssessor

Uncertain

2.8

M;.;M;.

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.6

D;D;D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.010

D;D;D;D

Sift4G

Benign

0.064

T;T;T;D

Polyphen

0.99

D;.;D;.

Vest4

0.71

MutPred

0.16

Gain of phosphorylation at G561 (P = 0.0369);.;Gain of phosphorylation at G561 (P = 0.0369);.;

MVP

0.66

MPC

1.1

ClinPred

0.95

GERP RS

5.3

Varity_R

0.57

gMVP

0.53

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over