14-23062958-T-A

Variant names:

• chr14-23062958-T-A
• rs370570553
• NM_001386863.1:c.2854A>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001386863.1(ACIN1):​c.2854A>T​(p.Ile952Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,458,640 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. I952V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: ACIN1 NM_001386863.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19485041).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

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.2854A>T	p.Ile952Phe	missense	Exon 14 of 19	NP_001373792.1	S4R3H4
	ACIN1	NM_014977.4		c.3028A>T	p.Ile1010Phe	missense	Exon 14 of 19	NP_055792.2	Q9UKV3-1
	ACIN1	NM_001164814.2		c.2989A>T	p.Ile997Phe	missense	Exon 14 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.2854A>T	p.Ile952Phe	missense	Exon 14 of 19	ENSP00000474349.1	S4R3H4
	ACIN1	ENST00000262710.5	TSL:1	c.3028A>T	p.Ile1010Phe	missense	Exon 14 of 19	ENSP00000262710.1	Q9UKV3-1
	ACIN1	ENST00000555053.5	TSL:1	c.2989A>T	p.Ile997Phe	missense	Exon 14 of 19	ENSP00000451328.1	Q9UKV3-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1458640 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 725672

African (AFR) AF: 0.00 AC: 0 AN: 33252

American (AMR) AF: 0.00 AC: 0 AN: 43622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26000

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 85596

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111086

Other (OTH) AF: 0.00 AC: 0 AN: 60260

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Benign	0.030	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.2
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.17
Sift	Benign	0.058	T
Sift4G	Benign	0.35	T
Polyphen		0.96	D
Vest4		0.25
MutPred		0.29		Loss of sheet (P = 7e-04)
MVP		0.34
MPC		2.2
ClinPred		0.82	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.70
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs370570553; hg19: chr14-23532167;