rs10499031

chr6-100588958-C-G

Variant summary

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

The NM_006828.4(ASCC3):c.5550+676G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0782 in 152,030 control chromosomes in the GnomAD database, including 588 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 0.078 (588 hom., cov: 32)
• Consequence: ASCC3 NM_006828.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASCC3	NM_006828.4	c.5550+676G>C		intron_variant		ENST00000369162.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASCC3	ENST00000369162.7	c.5550+676G>C		intron_variant		5	NM_006828.4	P1

Frequencies

GnomAD3 genomes AF: 0.0783 AC: 11895 AN: 151912 Hom.: 588 Cov.: 32

Gnomad AFR AF: 0.0336

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0540

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0680

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0923

Gnomad OTH AF: 0.0860

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

GnomAD4 genome AF: 0.0782 AC: 11889 AN: 152030 Hom.: 588 Cov.: 32 AF XY: 0.0804 AC XY: 5972 AN XY: 74322

Gnomad4 AFR AF: 0.0335

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.0540

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.0680

Gnomad4 NFE AF: 0.0923

Gnomad4 OTH AF: 0.0856

Alfa AF: 0.0818 Hom.: 67

Bravo AF: 0.0760

Asia WGS AF: 0.125 AC: 436 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.78
Dann	Benign	0.72

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: rs10499031; hg19: chr6-101036834;