Variant rs3751501 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001386863.1(ACIN1):c.1259C>T(p.Ser420Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0542 in 1,614,112 control chromosomes in the GnomAD database, including 2,603 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.044 ( 193 hom., cov: 32)

Exomes 𝑓: 0.055 ( 2410 hom. )

Consequence

ACIN1
NM_001386863.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.29

Variant links:

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]

ACIN1 links:

LOC124903288 (HGNC:):

LOC124903288 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017047822).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACIN1	NM_001386863.1 linkuse as main transcript	c.1259C>T	p.Ser420Phe	missense_variant	6/19	ENST00000605057.6	NP_001373792.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ACIN1	ENST00000605057.6 linkuse as main transcript	c.1259C>T	p.Ser420Phe	missense_variant	6/19	1	NM_001386863.1	ENSP00000474349.1	S4R3H4
ACIN1	ENST00000262710.5 linkuse as main transcript	c.1433C>T	p.Ser478Phe	missense_variant	6/19	1		ENSP00000262710.1	Q9UKV3-1
ACIN1	ENST00000555053.5 linkuse as main transcript	c.1433C>T	p.Ser478Phe	missense_variant	6/19	1		ENSP00000451328.1	Q9UKV3-5
ACIN1	ENST00000457657.5 linkuse as main transcript	c.1313C>T	p.Ser438Phe	missense_variant	5/18	5		ENSP00000405677.1	E7EQT4

Frequencies

GnomAD3 genomes

AF:

0.0444

AC:

6750

AN:

152124

Hom.:

193

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0167

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.0407

Gnomad ASJ

AF:

0.0464

Gnomad EAS

AF:

0.128

Gnomad SAS

AF:

0.0418

Gnomad FIN

AF:

0.0332

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0573

Gnomad OTH

AF:

0.0521

GnomAD3 exomes

AF:

0.0526

AC:

13216

AN:

251316

Hom.:

426

AF XY:

0.0522

AC XY:

7096

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.0166

Gnomad AMR exome

AF:

0.0357

Gnomad ASJ exome

AF:

0.0472

Gnomad EAS exome

AF:

0.125

Gnomad SAS exome

AF:

0.0341

Gnomad FIN exome

AF:

0.0336

Gnomad NFE exome

AF:

0.0602

Gnomad OTH exome

AF:

0.0531

GnomAD4 exome

AF:

0.0552

AC:

80661

AN:

1461870

Hom.:

2410

Cov.:

AF XY:

0.0548

AC XY:

39851

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0149

Gnomad4 AMR exome

AF:

0.0374

Gnomad4 ASJ exome

AF:

0.0460

Gnomad4 EAS exome

AF:

0.112

Gnomad4 SAS exome

AF:

0.0367

Gnomad4 FIN exome

AF:

0.0344

Gnomad4 NFE exome

AF:

0.0577

Gnomad4 OTH exome

AF:

0.0555

GnomAD4 genome

AF:

0.0443

AC:

6747

AN:

152242

Hom.:

193

Cov.:

AF XY:

0.0443

AC XY:

3300

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0166

Gnomad4 AMR

AF:

0.0406

Gnomad4 ASJ

AF:

0.0464

Gnomad4 EAS

AF:

0.128

Gnomad4 SAS

AF:

0.0429

Gnomad4 FIN

AF:

0.0332

Gnomad4 NFE

AF:

0.0573

Gnomad4 OTH

AF:

0.0516

Alfa

AF:

0.0576

Hom.:

692

Bravo

AF:

0.0438

TwinsUK

AF:

0.0612

AC:

227

ALSPAC

AF:

0.0599

AC:

231

ESP6500AA

AF:

0.0179

AC:

ESP6500EA

AF:

0.0574

AC:

494

ExAC

AF:

0.0535

AC:

6494

Asia WGS

AF:

0.0530

AC:

186

AN:

3478

EpiCase

AF:

0.0609

EpiControl

AF:

0.0598

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

.;T;.;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.91

D;D;D;D

MetaRNN

Benign

0.0017

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

.;N;.;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.98

.;N;N;N

REVEL

Benign

0.12

Sift

Uncertain

0.0010

.;D;D;D

Sift4G

Uncertain

0.023

D;D;D;D

Polyphen

0.98, 0.99

.;D;D;.

Vest4

0.11

MPC

0.13

ClinPred

0.017

GERP RS

5.4

Varity_R

0.12

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over