Genetic Variant NM_006828.4:c.5550+676G>C (chr6-100588958-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_006828.4(ASCC3):c.5550+676G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0782 in 152,030 control chromosomes in the GnomAD database, including 588 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 0.078 ( 588 hom., cov: 32)

Consequence

ASCC3
NM_006828.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.12

Publications

1 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: STRONG, LIMITED Submitted by: PanelApp Australia, G2P
intellectual disability
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ASCC3 links:

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new If you want to explore the variant's impact on the transcript NM_006828.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006828.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASCC3	NM_006828.4	MANE Select	c.5550+676G>C		intron	N/A	NP_006819.2	Q8N3C0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ASCC3	ENST00000369162.7	TSL:5 MANE Select	c.5550+676G>C	intron	N/A	ENSP00000358159.2	Q8N3C0-1
ASCC3	ENST00000930696.1		c.5565+676G>C	intron	N/A	ENSP00000600755.1
ASCC3	ENST00000930699.1		c.5565+676G>C	intron	N/A	ENSP00000600758.1

Frequencies

GnomAD3 genomes

AF:

0.0783

AC:

11895

AN:

151912

Hom.:

588

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0336

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.104

Gnomad ASJ

AF:

0.0540

Gnomad EAS

AF:

0.151

Gnomad SAS

AF:

0.149

Gnomad FIN

AF:

0.0680

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0923

Gnomad OTH

AF:

0.0860

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0782

AC:

11889

AN:

152030

Hom.:

588

Cov.:

AF XY:

0.0804

AC XY:

5972

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.0335

AC:

1392

AN:

41494

American (AMR)

AF:

0.104

AC:

1583

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0540

AC:

187

AN:

3466

East Asian (EAS)

AF:

0.150

AC:

778

AN:

5170

South Asian (SAS)

AF:

0.148

AC:

715

AN:

4824

European-Finnish (FIN)

AF:

0.0680

AC:

718

AN:

10560

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0923

AC:

6270

AN:

67932

Other (OTH)

AF:

0.0856

AC:

180

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

545

1089

1634

2178

2723

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

276

414

552

690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0818

Hom.:

Bravo

AF:

0.0760

Asia WGS

AF:

0.125

AC:

436

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.78

(source)

DANN

Benign

0.72

PhyloP100

-1.1

Mutation Taster

=100/0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over