rs239229

Positions:

• chr6-100658099-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006828.4(ASCC3):​c.2704-2281A>G 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 151,182 control chromosomes in the GnomAD database, including 24,190 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 (24190 hom., cov: 31)
• Consequence: ASCC3 NM_006828.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASCC3	NM_006828.4	c.2704-2281A>G		intron_variant		ENST00000369162.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASCC3	ENST00000369162.7	c.2704-2281A>G		intron_variant		5	NM_006828.4	P1
ASCC3	ENST00000324696.8	c.*2406-2281A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85039 AN: 151064 Hom.: 24153 Cov.: 31

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.563 AC: 85123 AN: 151182 Hom.: 24190 Cov.: 31 AF XY: 0.561 AC XY: 41477 AN XY: 73890

Gnomad4 AFR AF: 0.596

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.573

Alfa AF: 0.556 Hom.: 3396

Bravo AF: 0.579

Asia WGS AF: 0.558 AC: 1937 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.85
DANN	Benign	0.51

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

LitVar

Other links and lift over

dbSNP: rs239229; hg19: chr6-101105975;