NM_006828.4:c.2152-1159G>A

Variant names:

• chr6-100680911-C-T
• rs239189
• NM_006828.4:c.2152-1159G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006828.4(ASCC3):​c.2152-1159G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 151,928 control chromosomes in the GnomAD database, including 24,331 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 0.56 (24331 hom., cov: 32)
• Consequence: ASCC3 NM_006828.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.405
• Publications: 4 publications found

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

ACMG classification

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 = 0.706 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.2152-1159G>A		intron	N/A	NP_006819.2	Q8N3C0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASCC3	ENST00000369162.7	TSL:5 MANE Select	c.2152-1159G>A		intron	N/A	ENSP00000358159.2	Q8N3C0-1
	ASCC3	ENST00000930696.1		c.2167-1159G>A		intron	N/A	ENSP00000600755.1
	ASCC3	ENST00000930699.1		c.2167-1159G>A		intron	N/A	ENSP00000600758.1

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85515 AN: 151812 Hom.: 24294 Cov.: 32

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.563 AC: 85599 AN: 151928 Hom.: 24331 Cov.: 32 AF XY: 0.562 AC XY: 41747 AN XY: 74244

African (AFR) AF: 0.597 AC: 24726 AN: 41406

American (AMR) AF: 0.623 AC: 9521 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1927 AN: 3470

East Asian (EAS) AF: 0.726 AC: 3741 AN: 5154

South Asian (SAS) AF: 0.404 AC: 1945 AN: 4820

European-Finnish (FIN) AF: 0.540 AC: 5693 AN: 10538

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 36007 AN: 67950

Other (OTH) AF: 0.570 AC: 1201 AN: 2106

Alfa AF: 0.558 Hom.: 3557

Bravo AF: 0.578

Asia WGS AF: 0.564 AC: 1957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.8
DANN	Benign	0.64
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs239189; hg19: chr6-101128787;