rs12206945

chr6-100570156-A-Gchr6-100570156-A-T

Variant summary

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

The NM_006828.4(ASCC3):c.5550+19478T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 151,946 control chromosomes in the GnomAD database, including 17,278 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 0.47 (17278 hom., cov: 31)
• Consequence: ASCC3 NM_006828.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18

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=-1.06).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASCC3	NM_006828.4	c.5550+19478T>C		intron_variant		ENST00000369162.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASCC3	ENST00000369162.7	c.5550+19478T>C		intron_variant		5	NM_006828.4	P1

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71829 AN: 151828 Hom.: 17257 Cov.: 31

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.473 AC: 71886 AN: 151946 Hom.: 17278 Cov.: 31 AF XY: 0.473 AC XY: 35159 AN XY: 74258

Gnomad4 AFR AF: 0.513

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.454

Alfa AF: 0.459 Hom.: 7671

Bravo AF: 0.461

Asia WGS AF: 0.452 AC: 1576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.43
Dann	Benign	0.47

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: rs12206945; hg19: chr6-101018032;