rs9373571

Variant names:

• chr6-100685958-T-A
• rs9373571
• NM_006828.4:c.2152-6206A>T

Variant summary

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

The NM_006828.4(ASCC3):​c.2152-6206A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,044 control chromosomes in the GnomAD database, including 10,860 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 0.35 (10860 hom., cov: 32)
• Consequence: ASCC3 NM_006828.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.475
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASCC3	NM_006828.4	c.2152-6206A>T		intron_variant	Intron 13 of 41	ENST00000369162.7	NP_006819.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASCC3	ENST00000369162.7	c.2152-6206A>T		intron_variant	Intron 13 of 41	5	NM_006828.4	ENSP00000358159.2
ASCC3	ENST00000324696.8	n.*1854-6206A>T		intron_variant	Intron 12 of 19	2		ENSP00000320252.4

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52864 AN: 151926 Hom.: 10855 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.348 AC: 52883 AN: 152044 Hom.: 10860 Cov.: 32 AF XY: 0.344 AC XY: 25583 AN XY: 74300

African (AFR) AF: 0.132 AC: 5489 AN: 41528

American (AMR) AF: 0.435 AC: 6635 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1700 AN: 3466

East Asian (EAS) AF: 0.228 AC: 1178 AN: 5162

South Asian (SAS) AF: 0.219 AC: 1055 AN: 4824

European-Finnish (FIN) AF: 0.432 AC: 4556 AN: 10556

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.451 AC: 30650 AN: 67932

Other (OTH) AF: 0.394 AC: 831 AN: 2108

Alfa AF: 0.391 Hom.: 1555

Bravo AF: 0.342

Asia WGS AF: 0.228 AC: 794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.5
DANN	Benign	0.74
PhyloP100		0.47
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: rs9373571; hg19: chr6-101133834;