6-100858107-A-T

Variant names:

• chr6-100858107-A-T
• rs846793
• ENST00000369143.2:c.*1001T>A

Variant summary

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

The NM_022091.5(ASCC3):​c.*1001T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.949 in 348,668 control chromosomes in the GnomAD database, including 157,131 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 (67144 hom., cov: 32)
  • Exomes 𝑓: 0.96 (89987 hom.)
• Consequence: ASCC3 NM_022091.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.668
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022091.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASCC3	NM_006828.4	MANE Select	c.241+5957T>A		intron	N/A	NP_006819.2	Q8N3C0-1
	ASCC3	NM_022091.5		c.*1001T>A		3_prime_UTR	Exon 4 of 4	NP_071374.1	Q8N3C0-3
	ASCC3	NM_001284271.2		c.241+5957T>A		intron	N/A	NP_001271200.1	Q8N3C0-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASCC3	ENST00000369143.2	TSL:1	c.*1001T>A		3_prime_UTR	Exon 4 of 4	ENSP00000358139.2	Q8N3C0-3
	ASCC3	ENST00000369162.7	TSL:5 MANE Select	c.241+5957T>A		intron	N/A	ENSP00000358159.2	Q8N3C0-1
	ASCC3	ENST00000522650.5	TSL:1	c.241+5957T>A		intron	N/A	ENSP00000430769.1	Q8N3C0-4

Frequencies

GnomAD3 genomes AF: 0.939 AC: 142692 AN: 151886 Hom.: 67092 Cov.: 32

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.961

Gnomad AMR AF: 0.971

Gnomad ASJ AF: 0.976

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.955

Gnomad FIN AF: 0.918

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.953

Gnomad OTH AF: 0.954

GnomAD4 exome AF: 0.956 AC: 188105 AN: 196664 Hom.: 89987 Cov.: 4 AF XY: 0.957 AC XY: 88781 AN XY: 92756

African (AFR) AF: 0.881 AC: 3275 AN: 3718

American (AMR) AF: 0.980 AC: 194 AN: 198

Ashkenazi Jewish (ASJ) AF: 0.976 AC: 1156 AN: 1184

East Asian (EAS) AF: 0.979 AC: 840 AN: 858

South Asian (SAS) AF: 0.963 AC: 3541 AN: 3676

European-Finnish (FIN) AF: 0.906 AC: 58 AN: 64

Middle Eastern (MID) AF: 0.959 AC: 393 AN: 410

European-Non Finnish (NFE) AF: 0.957 AC: 172657 AN: 180330

Other (OTH) AF: 0.962 AC: 5991 AN: 6226

GnomAD4 genome AF: 0.939 AC: 142802 AN: 152004 Hom.: 67144 Cov.: 32 AF XY: 0.938 AC XY: 69715 AN XY: 74298

African (AFR) AF: 0.900 AC: 37340 AN: 41498

American (AMR) AF: 0.971 AC: 14807 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.976 AC: 3383 AN: 3466

East Asian (EAS) AF: 0.976 AC: 5064 AN: 5186

South Asian (SAS) AF: 0.956 AC: 4601 AN: 4814

European-Finnish (FIN) AF: 0.918 AC: 9705 AN: 10568

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.953 AC: 64733 AN: 67906

Other (OTH) AF: 0.955 AC: 2011 AN: 2106

Alfa AF: 0.941 Hom.: 7867

Bravo AF: 0.942

Asia WGS AF: 0.960 AC: 3330 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.7
DANN	Benign	0.50
PhyloP100		0.67
Mutation Taster		=99/1	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: rs846793; hg19: chr6-101305983;