rs1022983752

Variant names:

• chr10-72102392-G-C
• rs1022983752
• NM_001198800.3:c.958-4942C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001198799.3(ASCC1):​c.1180C>G​(p.Gln394Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000323 in 1,549,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ASCC1 NM_001198799.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.484
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09204227).
• BP6: Variant 10-72102392-G-C is Benign according to our data. Variant chr10-72102392-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2917740.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198799.3. 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.958-4942C>G		intron	N/A	NP_001185729.1	Q8N9N2-2
	ASCC1	NM_001198799.3		c.1180C>G	p.Gln394Glu	missense	Exon 12 of 13	NP_001185728.1	Q8N9N2-1
	ASCC1	NM_001369085.1		c.1162C>G	p.Gln388Glu	missense	Exon 11 of 12	NP_001356014.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASCC1	ENST00000672957.1	MANE Select	c.958-4942C>G		intron	N/A	ENSP00000500935.1	Q8N9N2-2
	ASCC1	ENST00000342444.8	TSL:2	c.1180C>G	p.Gln394Glu	missense	Exon 12 of 13	ENSP00000339404.4	Q8N9N2-1
	ASCC1	ENST00000394915.7	TSL:5	c.1180C>G	p.Gln394Glu	missense	Exon 12 of 12	ENSP00000378373.3	Q8N9N2-1

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151722 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000732

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1398140 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 689590

African (AFR) AF: 0.00 AC: 0 AN: 31548

American (AMR) AF: 0.00 AC: 0 AN: 35690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25156

East Asian (EAS) AF: 0.00 AC: 0 AN: 35716

South Asian (SAS) AF: 0.00 AC: 0 AN: 79200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1078682

Other (OTH) AF: 0.00 AC: 0 AN: 58104

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151722 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 74136

African (AFR) AF: 0.0000732 AC: 3 AN: 40980

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	3.3
DANN	Benign	0.92
DEOGEN2	Benign	0.0023	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.99	L
PhyloP100		0.48
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.052
Sift	Benign	0.048	D
Sift4G	Benign	0.070	T
Polyphen		0.61	P
Vest4		0.21
MVP		0.23
MPC		0.18
ClinPred		0.13	T
GERP RS		1.1
Varity_R		0.13
gMVP		0.19
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1022983752; hg19: chr10-73862150;