Genetic Variant SHISA3:p.Ala69Asp (chr4-42398262-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001080505.3(SHISA3):c.206C>A(p.Ala69Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SHISA3
NM_001080505.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.684

Publications

0 publications found

Variant links:

Genes affected

SHISA3 (HGNC:25159): (shisa family member 3) This gene encodes a single-transmembrane protein which is one of nine members of a family of transmembrane adaptors that modulate both WNT and FGF signaling by blocking the maturation and transport of their receptors to the cell surface. Members of this family contain an N-terminal cysteine-rich domain with a distinct cysteine pattern, a single transmembrane domain, and a C-terminal proline-rich, low complexity region. The encoded protein acts as a tumor suppressor by accelerating beta-catenin degradation. [provided by RefSeq, Jul 2017]

SHISA3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19287333).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080505.3. 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
	SHISA3	NM_001080505.3	MANE Select	c.206C>A	p.Ala69Asp	missense	Exon 1 of 2	NP_001073974.1	A0PJX4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHISA3	ENST00000319234.5	TSL:1 MANE Select	c.206C>A	p.Ala69Asp	missense	Exon 1 of 2	ENSP00000326445.4	A0PJX4
	SHISA3	ENST00000909498.1		c.206C>A	p.Ala69Asp	missense	Exon 1 of 2	ENSP00000579557.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1417092

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

701064

African (AFR)

AF:

0.00

AC:

AN:

32320

American (AMR)

AF:

0.00

AC:

AN:

38616

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25364

East Asian (EAS)

AF:

0.00

AC:

AN:

36956

South Asian (SAS)

AF:

0.00

AC:

AN:

80844

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48848

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1089714

Other (OTH)

AF:

0.00

AC:

AN:

58730

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.32

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.47

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

0.68

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-2.0

REVEL

Benign

0.15

Sift

Benign

0.033

Sift4G

Uncertain

0.027

Polyphen

0.32

Vest4

0.47

MutPred

0.33

Gain of loop (P = 0.1069)

MVP

0.24

MPC

0.60

ClinPred

0.68

GERP RS

3.2

Varity_R

0.45

gMVP

0.86

Mutation Taster

=73/27

polymorphism

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over