10-72097387-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001198800.3(ASCC1):c.1021A>G(p.Thr341Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T341T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ASCC1 NM_001198800.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.64

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.094833225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASCC1	NM_001198800.3	c.1021A>G	p.Thr341Ala	missense_variant	10/10	ENST00000672957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASCC1	ENST00000672957.1	c.1021A>G	p.Thr341Ala	missense_variant	10/10		NM_001198800.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

The c.1021A>G (p.T341A) alteration is located in exon 10 (coding exon 9) of the ASCC1 gene. This alteration results from a A to G substitution at nucleotide position 1021, causing the threonine (T) at amino acid position 341 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
Cadd	Benign	15
Dann	Uncertain	0.98
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.78	T;.;.
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.095	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.62	D;D;D;D;D;D
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.063
Sift	Uncertain	0.029	D;D;D
Sift4G	Benign	0.14	T;T;T
Vest4		0.057
MVP		0.29
ClinPred		0.32	T
GERP RS		-0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-73857145;