rs12206945

Variant names:

• chr6-100570156-A-G
• rs12206945
• NM_006828.4:c.5550+19478T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-100570156-A-G
• chr6-100570156-A-T

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+19478T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 151,946 control chromosomes in the GnomAD database, including 17,278 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 0.47 (17278 hom., cov: 31)
• Consequence: ASCC3 NM_006828.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18
• Publications: 5 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=-1.06).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASCC3	NM_006828.4	c.5550+19478T>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+19478T>C		intron_variant	Intron 36 of 41	5	NM_006828.4	ENSP00000358159.2

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71829 AN: 151828 Hom.: 17257 Cov.: 31

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.473 AC: 71886 AN: 151946 Hom.: 17278 Cov.: 31 AF XY: 0.473 AC XY: 35159 AN XY: 74258

African (AFR) AF: 0.513 AC: 21266 AN: 41430

American (AMR) AF: 0.391 AC: 5975 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1548 AN: 3472

East Asian (EAS) AF: 0.274 AC: 1417 AN: 5166

South Asian (SAS) AF: 0.620 AC: 2983 AN: 4814

European-Finnish (FIN) AF: 0.472 AC: 4969 AN: 10534

Middle Eastern (MID) AF: 0.390 AC: 114 AN: 292

European-Non Finnish (NFE) AF: 0.477 AC: 32404 AN: 67956

Other (OTH) AF: 0.454 AC: 957 AN: 2110

Alfa AF: 0.460 Hom.: 8504

Bravo AF: 0.461

Asia WGS AF: 0.452 AC: 1576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.43
DANN	Benign	0.47
PhyloP100		-2.2
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: rs12206945; hg19: chr6-101018032;