rs10499031

Variant names:

• chr6-100588958-C-G
• rs10499031
• NM_006828.4:c.5550+676G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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 (EAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASCC3	NM_006828.4	c.5550+676G>C		intron_variant	Intron 36 of 41	ENST00000369162.7	NP_006819.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASCC3	ENST00000369162.7	c.5550+676G>C		intron_variant	Intron 36 of 41	5	NM_006828.4	ENSP00000358159.2

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

African (AFR) AF: 0.0335 AC: 1392 AN: 41494

American (AMR) AF: 0.104 AC: 1583 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0540 AC: 187 AN: 3466

East Asian (EAS) AF: 0.150 AC: 778 AN: 5170

South Asian (SAS) AF: 0.148 AC: 715 AN: 4824

European-Finnish (FIN) AF: 0.0680 AC: 718 AN: 10560

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0923 AC: 6270 AN: 67932

Other (OTH) AF: 0.0856 AC: 180 AN: 2104

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
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: rs10499031; hg19: chr6-101036834;