dbSNP rs1473018571: SHISA5:p.Ala92Pro (chr3-48479217-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016479.6(SHISA5):c.274G>C(p.Ala92Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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. A92T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0050 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0017 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SHISA5
NM_016479.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.862

Variant links:

Genes affected

SHISA5 (HGNC:30376): (shisa family member 5) This gene encodes a member of the shisa family. The encoded protein is localized to the endoplasmic reticulum, and together with p53 induces apoptosis in a caspase-dependent manner. Alternative splicing results in multiple transcript variants. Related pseudogenes of this gene are found on chromosome X. [provided by RefSeq, Apr 2016]

SHISA5 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06813094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHISA5	NM_016479.6 link	c.274G>C	p.Ala92Pro	missense_variant	Exon 3 of 6	ENST00000296444.7	NP_057563.3	Q8N114-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHISA5	ENST00000296444.7 link	c.274G>C	p.Ala92Pro	missense_variant	Exon 3 of 6	1	NM_016479.6	ENSP00000296444.2		Q8N114-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

558

AN:

110902

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00689

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00789

Gnomad ASJ

AF:

0.00763

Gnomad EAS

AF:

0.00772

Gnomad SAS

AF:

0.00238

Gnomad FIN

AF:

0.000958

Gnomad MID

AF:

0.00510

Gnomad NFE

AF:

0.00401

Gnomad OTH

AF:

0.00429

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00171

AC:

2386

AN:

1397208

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

1156

AN XY:

693364

show subpopulations

Gnomad4 AFR exome

AF:

0.00192

Gnomad4 AMR exome

AF:

0.00635

Gnomad4 ASJ exome

AF:

0.00178

Gnomad4 EAS exome

AF:

0.00413

Gnomad4 SAS exome

AF:

0.00362

Gnomad4 FIN exome

AF:

0.00105

Gnomad4 NFE exome

AF:

0.00132

Gnomad4 OTH exome

AF:

0.00219

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00503

AC:

559

AN:

111034

Hom.:

Cov.:

AF XY:

0.00474

AC XY:

258

AN XY:

54458

show subpopulations

Gnomad4 AFR

AF:

0.00686

Gnomad4 AMR

AF:

0.00797

Gnomad4 ASJ

AF:

0.00763

Gnomad4 EAS

AF:

0.00774

Gnomad4 SAS

AF:

0.00239

Gnomad4 FIN

AF:

0.000958

Gnomad4 NFE

AF:

0.00401

Gnomad4 OTH

AF:

0.00423

Alfa

AF:

0.00305

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

2.6

DANN

Benign

0.95

DEOGEN2

Benign

0.086

.;T;.;.;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.59

T;T;.;.;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.068

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.77

.;N;.;.;.;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.96

.;N;N;N;N;N

REVEL

Benign

0.037

Sift

Benign

0.21

.;T;T;T;T;T

Sift4G

Benign

0.10

T;T;T;T;T;.

Polyphen

0.0010

.;B;.;.;.;.

Vest4

0.21

MutPred

0.32

.;Loss of helix (P = 0.0196);.;.;.;.;

MVP

0.13

MPC

0.18

ClinPred

0.0085

GERP RS

-2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.76

Splicing

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