Variant 6-100510092-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_006828.4(ASCC3):c.6301T>C(p.Cys2101Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ASCC3
NM_006828.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.40

Variant links:

Genes affected

ASCC3 (HGNC:18697): (activating signal cointegrator 1 complex subunit 3) This gene encodes a protein that belongs to a family of helicases that are involved in the ATP-dependent unwinding of nucleic acid duplexes. The encoded protein is the largest subunit of the activating signal cointegrator 1 complex that is involved in DNA repair and resistance to alkylation damage. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ASCC3 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;

PP2

Missense variant where missense usually causes diseases, ASCC3

BP4

Computational evidence support a benign effect (MetaRNN=0.081276625).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASCC3	NM_006828.4 linkuse as main transcript	c.6301T>C	p.Cys2101Arg	missense_variant	41/42	ENST00000369162.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASCC3	ENST00000369162.7 linkuse as main transcript	c.6301T>C	p.Cys2101Arg	missense_variant	41/42	5	NM_006828.4	P1	Q8N3C0-1
ASCC3	ENST00000518006.1 linkuse as main transcript	n.217T>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2024

The c.6301T>C (p.C2101R) alteration is located in exon 41 (coding exon 40) of the ASCC3 gene. This alteration results from a T to C substitution at nucleotide position 6301, causing the cysteine (C) at amino acid position 2101 to be replaced by an arginine (R). 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

0.061

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.0031

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.65

M_CAP

Benign

0.0087

MetaRNN

Benign

0.081

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-2.3

MutationTaster

Benign

0.92

PrimateAI

Benign

0.33

PROVEAN

Benign

3.4

REVEL

Benign

0.10

Sift

Benign

0.36

Sift4G

Benign

0.71

Polyphen

0.0

Vest4

0.33

MutPred

0.58

Gain of disorder (P = 0.0043);

MVP

0.13

MPC

0.43

ClinPred

0.087

GERP RS

0.33

Varity_R

0.070

gMVP

0.38

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over