6-100858107-A-T

Position:

• chr6-100858107-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000369143.2(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 ENST00000369143.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.668

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASCC3	NM_006828.4	c.241+5957T>A		intron_variant		ENST00000369162.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASCC3	ENST00000369162.7	c.241+5957T>A		intron_variant		5	NM_006828.4	P1

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

Gnomad4 AFR exome AF: 0.881

Gnomad4 AMR exome AF: 0.980

Gnomad4 ASJ exome AF: 0.976

Gnomad4 EAS exome AF: 0.979

Gnomad4 SAS exome AF: 0.963

Gnomad4 FIN exome AF: 0.906

Gnomad4 NFE exome AF: 0.957

Gnomad4 OTH exome AF: 0.962

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

Gnomad4 AFR AF: 0.900

Gnomad4 AMR AF: 0.971

Gnomad4 ASJ AF: 0.976

Gnomad4 EAS AF: 0.976

Gnomad4 SAS AF: 0.956

Gnomad4 FIN AF: 0.918

Gnomad4 NFE AF: 0.953

Gnomad4 OTH AF: 0.955

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.7
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs846793; hg19: chr6-101305983;