rs240153

Variant names:

• chr6-100619259-A-C
• rs240153
• NM_006828.4:c.4785+5933T>G

Variant summary

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

The NM_006828.4(ASCC3):​c.4785+5933T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 151,940 control chromosomes in the GnomAD database, including 25,311 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 0.57 (25311 hom., cov: 32)
• Consequence: ASCC3 NM_006828.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 5 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASCC3	NM_006828.4	c.4785+5933T>G		intron_variant	Intron 30 of 41	ENST00000369162.7	NP_006819.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASCC3	ENST00000369162.7	c.4785+5933T>G		intron_variant	Intron 30 of 41	5	NM_006828.4	ENSP00000358159.2

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87246 AN: 151822 Hom.: 25277 Cov.: 32

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.575 AC: 87325 AN: 151940 Hom.: 25311 Cov.: 32 AF XY: 0.572 AC XY: 42516 AN XY: 74272

African (AFR) AF: 0.598 AC: 24775 AN: 41420

American (AMR) AF: 0.634 AC: 9657 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1944 AN: 3468

East Asian (EAS) AF: 0.727 AC: 3747 AN: 5152

South Asian (SAS) AF: 0.386 AC: 1861 AN: 4818

European-Finnish (FIN) AF: 0.550 AC: 5811 AN: 10562

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.551 AC: 37466 AN: 67968

Other (OTH) AF: 0.580 AC: 1222 AN: 2106

Alfa AF: 0.547 Hom.: 11637

Bravo AF: 0.589

Asia WGS AF: 0.559 AC: 1940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.65
PhyloP100		-1.1
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: rs240153; hg19: chr6-101067135;