6-100690714-C-T

Variant names:

• chr6-100690714-C-T
• rs10485138
• NM_006828.4:c.2152-10962G>A

Variant summary

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

The NM_006828.4(ASCC3):​c.2152-10962G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0282 in 152,128 control chromosomes in the GnomAD database, including 176 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 0.028 (176 hom., cov: 32)
• Consequence: ASCC3 NM_006828.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.715
• Publications: 2 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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006828.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASCC3	NM_006828.4	MANE Select	c.2152-10962G>A		intron	N/A	NP_006819.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASCC3	ENST00000369162.7	TSL:5 MANE Select	c.2152-10962G>A		intron	N/A	ENSP00000358159.2
	ASCC3	ENST00000324696.8	TSL:2	n.*1854-10962G>A		intron	N/A	ENSP00000320252.4

Frequencies

GnomAD3 genomes AF: 0.0282 AC: 4283 AN: 152012 Hom.: 176 Cov.: 32

Gnomad AFR AF: 0.00599

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0521

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.0880

Gnomad FIN AF: 0.0165

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0226

Gnomad OTH AF: 0.0316

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

GnomAD4 genome AF: 0.0282 AC: 4283 AN: 152128 Hom.: 176 Cov.: 32 AF XY: 0.0307 AC XY: 2285 AN XY: 74366

African (AFR) AF: 0.00597 AC: 248 AN: 41520

American (AMR) AF: 0.0522 AC: 797 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3470

East Asian (EAS) AF: 0.190 AC: 978 AN: 5158

South Asian (SAS) AF: 0.0885 AC: 427 AN: 4826

European-Finnish (FIN) AF: 0.0165 AC: 175 AN: 10600

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.0226 AC: 1537 AN: 67958

Other (OTH) AF: 0.0303 AC: 64 AN: 2112

Alfa AF: 0.0288 Hom.: 24

Bravo AF: 0.0294

Asia WGS AF: 0.124 AC: 429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.0
DANN	Benign	0.68
PhyloP100		0.71
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: rs10485138; hg19: chr6-101138590;