chr6-100768226-C-T

Variant names:

• chr6-100768226-C-T
• rs9390679
• NM_006828.4:c.1396-881G>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.1396-881G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 151,886 control chromosomes in the GnomAD database, including 23,279 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 0.55 (23279 hom., cov: 32)
• Consequence: ASCC3 NM_006828.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 0 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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASCC3	NM_006828.4	c.1396-881G>A		intron_variant	Intron 8 of 41	ENST00000369162.7	NP_006819.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASCC3	ENST00000369162.7	c.1396-881G>A		intron_variant	Intron 8 of 41	5	NM_006828.4	ENSP00000358159.2
ASCC3	ENST00000522650.5	c.1396-881G>A		intron_variant	Intron 8 of 12	1		ENSP00000430769.1
ASCC3	ENST00000324696.8	n.*1098-881G>A		intron_variant	Intron 7 of 19	2		ENSP00000320252.4

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83374 AN: 151766 Hom.: 23260 Cov.: 32

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.549 AC: 83441 AN: 151886 Hom.: 23279 Cov.: 32 AF XY: 0.555 AC XY: 41192 AN XY: 74206

African (AFR) AF: 0.631 AC: 26140 AN: 41452

American (AMR) AF: 0.513 AC: 7825 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1639 AN: 3464

East Asian (EAS) AF: 0.726 AC: 3740 AN: 5150

South Asian (SAS) AF: 0.750 AC: 3616 AN: 4820

European-Finnish (FIN) AF: 0.498 AC: 5225 AN: 10502

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33725 AN: 67918

Other (OTH) AF: 0.516 AC: 1090 AN: 2112

Alfa AF: 0.523 Hom.: 2707

Bravo AF: 0.551

Asia WGS AF: 0.727 AC: 2522 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.8
DANN	Benign	0.34
PhyloP100		-0.018
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: rs9390679; hg19: chr6-101216102;