Genetic Variant NM_001386863.1:c.1259C>T (chr14-23080076-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

19 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ACIN1	NM_001386863.1 link	c.1259C>T	p.Ser420Phe	missense_variant	Exon 6 of 19	ENST00000605057.6	NP_001373792.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ACIN1	ENST00000605057.6 link	c.1259C>T	p.Ser420Phe	missense_variant	Exon 6 of 19	1	NM_001386863.1	ENSP00000474349.1	S4R3H4
ACIN1	ENST00000262710.5 link	c.1433C>T	p.Ser478Phe	missense_variant	Exon 6 of 19	1		ENSP00000262710.1	Q9UKV3-1
ACIN1	ENST00000555053.5 link	c.1433C>T	p.Ser478Phe	missense_variant	Exon 6 of 19	1		ENSP00000451328.1	Q9UKV3-5
ACIN1	ENST00000457657.5 link	c.1313C>T	p.Ser438Phe	missense_variant	Exon 5 of 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

GnomAD2 exomes

AF:

0.0526

AC:

13216

AN:

251316

AF XY:

0.0522

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 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

African (AFR)

AF:

0.0149

AC:

500

AN:

33480

American (AMR)

AF:

0.0374

AC:

1672

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0460

AC:

1203

AN:

26136

East Asian (EAS)

AF:

0.112

AC:

4433

AN:

39700

South Asian (SAS)

AF:

0.0367

AC:

3165

AN:

86256

European-Finnish (FIN)

AF:

0.0344

AC:

1840

AN:

53414

Middle Eastern (MID)

AF:

0.0581

AC:

335

AN:

5766

European-Non Finnish (NFE)

AF:

0.0577

AC:

64159

AN:

1111998

Other (OTH)

AF:

0.0555

AC:

3354

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

5110

10220

15330

20440

25550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2350

4700

7050

9400

11750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0443

AC:

6747

AN:

152242

Hom.:

193

Cov.:

AF XY:

0.0443

AC XY:

3300

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0166

AC:

689

AN:

41546

American (AMR)

AF:

0.0406

AC:

621

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0464

AC:

161

AN:

3472

East Asian (EAS)

AF:

0.128

AC:

662

AN:

5164

South Asian (SAS)

AF:

0.0429

AC:

207

AN:

4830

European-Finnish (FIN)

AF:

0.0332

AC:

352

AN:

10596

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0573

AC:

3896

AN:

68018

Other (OTH)

AF:

0.0516

AC:

109

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

330

661

991

1322

1652

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0566

Hom.:

1248

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

(source)

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

PhyloP100

4.3

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

Mutation Taster

=94/6

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over