rs6939613

Variant names:

• chr6-100743803-C-T
• rs6939613
• NM_006828.4:c.1738-18100G>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.1738-18100G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.94 in 152,208 control chromosomes in the GnomAD database, including 67,583 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 0.94 (67583 hom., cov: 31)
• Consequence: ASCC3 NM_006828.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.375
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASCC3	NM_006828.4	c.1738-18100G>A		intron_variant	Intron 10 of 41	ENST00000369162.7	NP_006819.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASCC3	ENST00000369162.7	c.1738-18100G>A		intron_variant	Intron 10 of 41	5	NM_006828.4	ENSP00000358159.2
ASCC3	ENST00000522650.5	c.1738-18100G>A		intron_variant	Intron 10 of 12	1		ENSP00000430769.1
ASCC3	ENST00000324696.8	n.*1440-18100G>A		intron_variant	Intron 9 of 19	2		ENSP00000320252.4

Frequencies

GnomAD3 genomes AF: 0.940 AC: 142990 AN: 152090 Hom.: 67541 Cov.: 31

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.976

Gnomad ASJ AF: 0.985

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.988

Gnomad FIN AF: 0.986

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.981

Gnomad OTH AF: 0.953

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

GnomAD4 genome AF: 0.940 AC: 143088 AN: 152208 Hom.: 67583 Cov.: 31 AF XY: 0.941 AC XY: 70053 AN XY: 74420

African (AFR) AF: 0.835 AC: 34661 AN: 41492

American (AMR) AF: 0.976 AC: 14924 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.985 AC: 3420 AN: 3472

East Asian (EAS) AF: 0.955 AC: 4944 AN: 5176

South Asian (SAS) AF: 0.988 AC: 4766 AN: 4826

European-Finnish (FIN) AF: 0.986 AC: 10456 AN: 10604

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.981 AC: 66703 AN: 68022

Other (OTH) AF: 0.954 AC: 2014 AN: 2112

Alfa AF: 0.947 Hom.: 8845

Bravo AF: 0.935

Asia WGS AF: 0.971 AC: 3371 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.61
DANN	Benign	0.26
PhyloP100		-0.38
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: rs6939613; hg19: chr6-101191679;