14-23064188-G-A

Position:

• chr14-23064188-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001386863.1(ACIN1):​c.2512C>T​(p.Arg838Cys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ACIN1 NM_001386863.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.88

Genes affected

ACIN1 (HGNC:17066): (apoptotic chromatin condensation inducer 1) Apoptosis is defined by several morphologic nuclear changes, including chromatin condensation and nuclear fragmentation. This gene encodes a nuclear protein that induces apoptotic chromatin condensation after activation by caspase-3, without inducing DNA fragmentation. This protein has also been shown to be a component of a splicing-dependent multiprotein exon junction complex (EJC) that is deposited at splice junctions on mRNAs, as a consequence of pre-mRNA splicing. It may thus be involved in mRNA metabolism associated with splicing. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33082235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACIN1	NM_001386863.1	c.2512C>T	p.Arg838Cys	missense_variant	12/19	ENST00000605057.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACIN1	ENST00000605057.6	c.2512C>T	p.Arg838Cys	missense_variant	12/19	1	NM_001386863.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 2023

The c.2686C>T (p.R896C) alteration is located in exon 12 (coding exon 12) of the ACIN1 gene. This alteration results from a C to T substitution at nucleotide position 2686, causing the arginine (R) at amino acid position 896 to be replaced by a cysteine (C). 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
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.082	T;.;.;.;D;.;.;.;T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Pathogenic	0.97	D;D;.;D;D;D;D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.33	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.2	D;D;D;.;D;D;D;D;D
REVEL	Benign	0.13
Sift	Uncertain	0.0050	D;D;D;.;D;D;D;D;D
Sift4G	Uncertain	0.016	D;D;D;D;D;D;D;D;.
Polyphen		1.0, 1.0, 1.0	.;D;D;.;D;D;D;.;.
Vest4		0.31
MutPred		0.23		.;.;.;.;Loss of solvent accessibility (P = 0.0329);.;.;.;.;
MVP		0.61
MPC		2.4
ClinPred		0.97	D
GERP RS		4.5
Varity_R		0.34
gMVP		0.18

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-23533397;