Genetic Variant SIVA1:p.Ala63Ala (chr14-104755700-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_006427.4(SIVA1):c.189C>T(p.Ala63Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 1,613,528 control chromosomes in the GnomAD database, including 102,285 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 0.35 ( 9569 hom., cov: 33)

Exomes 𝑓: 0.35 ( 92716 hom. )

Consequence

SIVA1
NM_006427.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.253

Variant links:

Genes affected

SIVA1 (HGNC:17712): (SIVA1 apoptosis inducing factor) This gene encodes an E3 ubiquitin ligase that regulates cell cycle progression, cell proliferation and apoptosis. The N-terminus of this protein binds to the cytoplasmic tail of the CD27 antigen, a member of the tumor necrosis factor receptor (TNFR) superfamily. In response to UV radiation-induced DNA damage, this protein has been shown to mediate the ubiquitination of proliferating cell nuclear antigen (PCNA), an important step in translesion DNA synthesis. [provided by RefSeq, Sep 2018]

SIVA1 links:

LOC107987209 (HGNC:):

LOC107987209 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP7

Synonymous conserved (PhyloP=-0.253 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIVA1	NM_006427.4 link	c.189C>T	p.Ala63Ala	synonymous_variant	Exon 2 of 4	ENST00000329967.11	NP_006418.2	O15304-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIVA1	ENST00000329967.11 link	c.189C>T	p.Ala63Ala	synonymous_variant	Exon 2 of 4	1	NM_006427.4	ENSP00000329213.6		O15304-1

Frequencies

GnomAD3 genomes

AF:

0.345

AC:

52452

AN:

151968

Hom.:

9571

Cov.:

show subpopulations

Gnomad AFR

AF:

0.271

Gnomad AMI

AF:

0.299

Gnomad AMR

AF:

0.447

Gnomad ASJ

AF:

0.305

Gnomad EAS

AF:

0.612

Gnomad SAS

AF:

0.507

Gnomad FIN

AF:

0.367

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.335

Gnomad OTH

AF:

0.346

GnomAD3 exomes

AF:

0.394

AC:

99069

AN:

251212

Hom.:

21079

AF XY:

0.391

AC XY:

53171

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.266

Gnomad AMR exome

AF:

0.523

Gnomad ASJ exome

AF:

0.295

Gnomad EAS exome

AF:

0.609

Gnomad SAS exome

AF:

0.467

Gnomad FIN exome

AF:

0.370

Gnomad NFE exome

AF:

0.334

Gnomad OTH exome

AF:

0.376

GnomAD4 exome

AF:

0.349

AC:

510120

AN:

1461440

Hom.:

92716

Cov.:

AF XY:

0.352

AC XY:

255677

AN XY:

727046

show subpopulations

Gnomad4 AFR exome

AF:

0.268

Gnomad4 AMR exome

AF:

0.510

Gnomad4 ASJ exome

AF:

0.301

Gnomad4 EAS exome

AF:

0.576

Gnomad4 SAS exome

AF:

0.462

Gnomad4 FIN exome

AF:

0.372

Gnomad4 NFE exome

AF:

0.327

Gnomad4 OTH exome

AF:

0.361

GnomAD4 genome

AF:

0.345

AC:

52484

AN:

152088

Hom.:

9569

Cov.:

AF XY:

0.352

AC XY:

26166

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.271

Gnomad4 AMR

AF:

0.447

Gnomad4 ASJ

AF:

0.305

Gnomad4 EAS

AF:

0.611

Gnomad4 SAS

AF:

0.506

Gnomad4 FIN

AF:

0.367

Gnomad4 NFE

AF:

0.335

Gnomad4 OTH

AF:

0.349

Alfa

AF:

0.338

Hom.:

17658

Bravo

AF:

0.346

Asia WGS

AF:

0.536

AC:

1863

AN:

3478

EpiCase

AF:

0.348

EpiControl

AF:

0.331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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