Genetic Variant ASCC1:c.958-5393G>A (chr10-72102843-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001198799.3(ASCC1):c.1159+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ASCC1
NM_001198799.3 splice_region, intron

Scores

Splicing: ADA: 0.00004912

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.361

Publications

0 publications found

Variant links:

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)

ASCC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 10-72102843-C-T is Benign according to our data. Variant chr10-72102843-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2428257.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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ASCC1	NM_001198800.3	MANE Select	c.958-5393G>A	intron	N/A	NP_001185729.1	Q8N9N2-2
ASCC1	NM_001198799.3		c.1159+7G>A	splice_region intron	N/A	NP_001185728.1	Q8N9N2-1
ASCC1	NM_001369085.1		c.1141+7G>A	splice_region intron	N/A	NP_001356014.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ASCC1	ENST00000672957.1	MANE Select	c.958-5393G>A	intron	N/A	ENSP00000500935.1	Q8N9N2-2
ASCC1	ENST00000342444.8	TSL:2	c.1159+7G>A	splice_region intron	N/A	ENSP00000339404.4	Q8N9N2-1
ASCC1	ENST00000394915.7	TSL:5	c.1159+7G>A	splice_region intron	N/A	ENSP00000378373.3	Q8N9N2-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151788

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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

GnomAD2 exomes

AF:

0.0000374

AC:

AN:

53484

AF XY:

0.0000349

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000477

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000449

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

204770

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

115054

African (AFR)

AF:

0.00

AC:

AN:

4604

American (AMR)

AF:

0.00

AC:

AN:

9784

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5156

East Asian (EAS)

AF:

0.00

AC:

AN:

7082

South Asian (SAS)

AF:

0.00

AC:

AN:

42640

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9692

Middle Eastern (MID)

AF:

0.00

AC:

AN:

746

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

115456

Other (OTH)

AF:

0.00

AC:

AN:

9610

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

151788

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74130

African (AFR)

AF:

0.00

AC:

AN:

41252

American (AMR)

AF:

0.00

AC:

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5122

South Asian (SAS)

AF:

0.00

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67988

Other (OTH)

AF:

0.00

AC:

AN:

2086

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

3.7

(source)

DANN

Benign

0.23

PhyloP100

-0.36

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000049

dbscSNV1_RF

Benign

0.012

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over