Variant 6-100509468-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP2BP4_StrongBA1

The NM_006828.4(ASCC3):c.6527A>G(p.Tyr2176Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0609 in 1,614,024 control chromosomes in the GnomAD database, including 4,308 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.10 ( 1147 hom., cov: 32)

Exomes 𝑓: 0.057 ( 3161 hom. )

Consequence

ASCC3
NM_006828.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.70

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 Benign. Variant got -11 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ASCC3. . Gene score misZ 2.2287 (greater than the threshold 3.09). Trascript score misZ 3.3318 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017665625).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASCC3	NM_006828.4 linkuse as main transcript	c.6527A>G	p.Tyr2176Cys	missense_variant	42/42	ENST00000369162.7	NP_006819.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASCC3	ENST00000369162.7 linkuse as main transcript	c.6527A>G	p.Tyr2176Cys	missense_variant	42/42	5	NM_006828.4	ENSP00000358159	P1	Q8N3C0-1
ASCC3	ENST00000518006.1 linkuse as main transcript	n.443A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15356

AN:

152168

Hom.:

1144

Cov.:

show subpopulations

Gnomad AFR

AF:

0.207

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0831

Gnomad ASJ

AF:

0.0260

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.0763

Gnomad FIN

AF:

0.0666

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0494

Gnomad OTH

AF:

0.0888

GnomAD3 exomes

AF:

0.0796

AC:

20014

AN:

251438

Hom.:

1152

AF XY:

0.0753

AC XY:

10235

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.211

Gnomad AMR exome

AF:

0.0986

Gnomad ASJ exome

AF:

0.0291

Gnomad EAS exome

AF:

0.159

Gnomad SAS exome

AF:

0.0777

Gnomad FIN exome

AF:

0.0637

Gnomad NFE exome

AF:

0.0505

Gnomad OTH exome

AF:

0.0727

GnomAD4 exome

AF:

0.0568

AC:

82961

AN:

1461738

Hom.:

3161

Cov.:

AF XY:

0.0570

AC XY:

41472

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.212

Gnomad4 AMR exome

AF:

0.0999

Gnomad4 ASJ exome

AF:

0.0280

Gnomad4 EAS exome

AF:

0.131

Gnomad4 SAS exome

AF:

0.0764

Gnomad4 FIN exome

AF:

0.0624

Gnomad4 NFE exome

AF:

0.0460

Gnomad4 OTH exome

AF:

0.0654

GnomAD4 genome

AF:

0.101

AC:

15376

AN:

152286

Hom.:

1147

Cov.:

AF XY:

0.0997

AC XY:

7423

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.207

Gnomad4 AMR

AF:

0.0831

Gnomad4 ASJ

AF:

0.0260

Gnomad4 EAS

AF:

0.145

Gnomad4 SAS

AF:

0.0767

Gnomad4 FIN

AF:

0.0666

Gnomad4 NFE

AF:

0.0495

Gnomad4 OTH

AF:

0.0865

Alfa

AF:

0.0601

Hom.:

958

Bravo

AF:

0.107

TwinsUK

AF:

0.0423

AC:

157

ALSPAC

AF:

0.0470

AC:

181

ESP6500AA

AF:

0.195

AC:

860

ESP6500EA

AF:

0.0463

AC:

398

ExAC

AF:

0.0820

AC:

9959

Asia WGS

AF:

0.123

AC:

429

AN:

3478

EpiCase

AF:

0.0550

EpiControl

AF:

0.0530

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.053

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.0018

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.5

MutationTaster

Benign

0.61

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.9

REVEL

Benign

0.11

Sift

Benign

0.18

Sift4G

Benign

0.13

Polyphen

0.54

Vest4

0.14

MPC

0.31

ClinPred

0.042

GERP RS

4.8

Varity_R

0.15

gMVP

0.39

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over