14-23061366-C-G

Variant names:

• chr14-23061366-C-G
• rs939544228
• NM_001386863.1:c.3356G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001386863.1(ACIN1):​c.3356G>C​(p.Arg1119Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1119Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ACIN1 NM_001386863.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.43
• Publications: 1 publications found

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]

ENSG00000288795 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.268844).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386863.1. 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
	ACIN1	NM_001386863.1	MANE Select	c.3356G>C	p.Arg1119Pro	missense	Exon 17 of 19	NP_001373792.1	S4R3H4
	ACIN1	NM_014977.4		c.3530G>C	p.Arg1177Pro	missense	Exon 17 of 19	NP_055792.2	Q9UKV3-1
	ACIN1	NM_001164814.2		c.3491G>C	p.Arg1164Pro	missense	Exon 17 of 19	NP_001158286.2	Q9UKV3-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACIN1	ENST00000605057.6	TSL:1 MANE Select	c.3356G>C	p.Arg1119Pro	missense	Exon 17 of 19	ENSP00000474349.1	S4R3H4
	ACIN1	ENST00000262710.5	TSL:1	c.3530G>C	p.Arg1177Pro	missense	Exon 17 of 19	ENSP00000262710.1	Q9UKV3-1
	ACIN1	ENST00000555053.5	TSL:1	c.3491G>C	p.Arg1164Pro	missense	Exon 17 of 19	ENSP00000451328.1	Q9UKV3-5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.091	T
Eigen	Benign	0.063
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		6.4
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.16
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.039	D
Polyphen		0.055	B
Vest4		0.50
MutPred		0.28		Gain of glycosylation at R1177 (P = 0.0093)
MVP		0.48
MPC		2.5
ClinPred		0.96	D
GERP RS		3.9
Varity_R		0.74
gMVP		0.63
Mutation Taster		=31/69	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs939544228; hg19: chr14-23530575;