rs6939613

Positions:

• chr6-100743803-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	Protein	UniProt
ASCC3	NM_006828.4	c.1738-18100G>A		intron_variant		ENST00000369162.7	NP_006819.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASCC3	ENST00000369162.7	c.1738-18100G>A		intron_variant		5	NM_006828.4	ENSP00000358159	P1
ASCC3	ENST00000522650.5	c.1738-18100G>A		intron_variant		1		ENSP00000430769
ASCC3	ENST00000324696.8	c.*1440-18100G>A		intron_variant, NMD_transcript_variant		2		ENSP00000320252

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

Gnomad4 AFR AF: 0.835

Gnomad4 AMR AF: 0.976

Gnomad4 ASJ AF: 0.985

Gnomad4 EAS AF: 0.955

Gnomad4 SAS AF: 0.988

Gnomad4 FIN AF: 0.986

Gnomad4 NFE AF: 0.981

Gnomad4 OTH AF: 0.954

Alfa AF: 0.951 Hom.: 8567

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

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: rs6939613; hg19: chr6-101191679;