rs1300718230

Variant names:

• chr10-72097391-C-T
• rs1300718230
• NM_001198800.3:c.1017G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001198800.3(ASCC1):​c.1017G>A​(p.Arg339Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ASCC1 NM_001198800.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.643
• Publications: 0 publications found

Genes affected

ASCC1 (HGNC:24268): (activating signal cointegrator 1 complex subunit 1) This gene encodes a subunit of the activating signal cointegrator 1 (ASC-1) complex. The ASC-1 complex is a transcriptional coactivator that plays an important role in gene transactivation by multiple transcription factors including activating protein 1 (AP-1), nuclear factor kappa-B (NF-kB) and serum response factor (SRF). The encoded protein contains an N-terminal KH-type RNA-binding motif which is required for AP-1 transactivation by the ASC-1 complex. Mutations in this gene are associated with Barrett esophagus and esophageal adenocarcinoma. Alternatively spliced transcripts encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

ASCC1 Gene-Disease associations (from GenCC):

• spinal muscular atrophy with congenital bone fractures 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Illumina, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 10-72097391-C-T is Benign according to our data. Variant chr10-72097391-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2825574.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.643 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198800.3. 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
	ASCC1	NM_001198800.3	MANE Select	c.1017G>A	p.Arg339Arg	synonymous	Exon 10 of 10	NP_001185729.1	Q8N9N2-2
	ASCC1	NM_001198798.2		c.1017G>A	p.Arg339Arg	synonymous	Exon 10 of 10	NP_001185727.1	Q8N9N2-2
	ASCC1	NM_001369093.1		c.1017G>A	p.Arg339Arg	synonymous	Exon 10 of 10	NP_001356022.1	Q8N9N2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASCC1	ENST00000672957.1	MANE Select	c.1017G>A	p.Arg339Arg	synonymous	Exon 10 of 10	ENSP00000500935.1	Q8N9N2-2
	ASCC1	ENST00000902262.1		c.1101G>A	p.Arg367Arg	synonymous	Exon 11 of 11	ENSP00000572321.1
	ASCC1	ENST00000672774.1		c.1077G>A	p.Arg359Arg	synonymous	Exon 11 of 11	ENSP00000500488.1	A0A5F9ZHP1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251484 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461718 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727160

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111884

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	8.1
DANN	Benign	0.55
PhyloP100		0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1300718230; hg19: chr10-73857149;