Genetic Variant ENST00000369143.2:c.*1001T>A (chr6-100858107-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000369143.2(ASCC3):c.*1001T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.949 in 348,668 control chromosomes in the GnomAD database, including 157,131 homozygotes. 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: 𝑓 0.94 ( 67144 hom., cov: 32)

Exomes 𝑓: 0.96 ( 89987 hom. )

Consequence

ASCC3
ENST00000369143.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.668

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

intellectual developmental disorder, autosomal recessive 81
Inheritance: AR Classification: LIMITED Submitted by: G2P
intellectual disability
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ASCC3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASCC3	NM_006828.4 link	c.241+5957T>A		intron_variant	Intron 3 of 41	ENST00000369162.7	NP_006819.2	Q8N3C0-1B4DR60

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASCC3	ENST00000369162.7 link	c.241+5957T>A		intron_variant	Intron 3 of 41	5	NM_006828.4	ENSP00000358159.2		Q8N3C0-1

Frequencies

GnomAD3 genomes

AF:

0.939

AC:

142692

AN:

151886

Hom.:

67092

Cov.:

show subpopulations

Gnomad AFR

AF:

0.900

Gnomad AMI

AF:

0.961

Gnomad AMR

AF:

0.971

Gnomad ASJ

AF:

0.976

Gnomad EAS

AF:

0.977

Gnomad SAS

AF:

0.955

Gnomad FIN

AF:

0.918

Gnomad MID

AF:

0.959

Gnomad NFE

AF:

0.953

Gnomad OTH

AF:

0.954

GnomAD4 exome

AF:

0.956

AC:

188105

AN:

196664

Hom.:

89987

Cov.:

AF XY:

0.957

AC XY:

88781

AN XY:

92756

show subpopulations

African (AFR)

AF:

0.881

AC:

3275

AN:

3718

American (AMR)

AF:

0.980

AC:

194

AN:

198

Ashkenazi Jewish (ASJ)

AF:

0.976

AC:

1156

AN:

1184

East Asian (EAS)

AF:

0.979

AC:

840

AN:

858

South Asian (SAS)

AF:

0.963

AC:

3541

AN:

3676

European-Finnish (FIN)

AF:

0.906

AC:

AN:

Middle Eastern (MID)

AF:

0.959

AC:

393

AN:

410

European-Non Finnish (NFE)

AF:

0.957

AC:

172657

AN:

180330

Other (OTH)

AF:

0.962

AC:

5991

AN:

6226

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

388

775

1163

1550

1938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.939

AC:

142802

AN:

152004

Hom.:

67144

Cov.:

AF XY:

0.938

AC XY:

69715

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.900

AC:

37340

AN:

41498

American (AMR)

AF:

0.971

AC:

14807

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.976

AC:

3383

AN:

3466

East Asian (EAS)

AF:

0.976

AC:

5064

AN:

5186

South Asian (SAS)

AF:

0.956

AC:

4601

AN:

4814

European-Finnish (FIN)

AF:

0.918

AC:

9705

AN:

10568

Middle Eastern (MID)

AF:

0.959

AC:

282

AN:

294

European-Non Finnish (NFE)

AF:

0.953

AC:

64733

AN:

67906

Other (OTH)

AF:

0.955

AC:

2011

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

456

912

1368

1824

2280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.941

Hom.:

7867

Bravo

AF:

0.942

Asia WGS

AF:

0.960

AC:

3330

AN:

3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

2.7

(source)

DANN

Benign

0.50

PhyloP100

0.67

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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ENST00000369143.2:c.*1001T>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over