Genetic Variant SHISA3:p.Ala68Thr (chr4-42398258-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001080505.3(SHISA3):c.202G>A(p.Ala68Thr) 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: 2.70

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2847982).

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.202G>A	p.Ala68Thr	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.202G>A	p.Ala68Thr	missense	Exon 1 of 2	ENSP00000326445.4	A0PJX4
	SHISA3	ENST00000909498.1		c.202G>A	p.Ala68Thr	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:

1417980

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

701594

African (AFR)

AF:

0.00

AC:

AN:

32336

American (AMR)

AF:

0.00

AC:

AN:

38762

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25374

East Asian (EAS)

AF:

0.00

AC:

AN:

37006

South Asian (SAS)

AF:

0.00

AC:

AN:

80890

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48924

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1090228

Other (OTH)

AF:

0.00

AC:

AN:

58756

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

0.20

BayesDel_addAF

Benign

-0.040

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.071

Eigen

Benign

0.16

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.85

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.28

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

2.7

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.38

REVEL

Benign

0.22

Sift

Benign

0.45

Sift4G

Benign

0.98

Polyphen

1.0

Vest4

0.16

MutPred

0.31

Gain of glycosylation at A68 (P = 0.0724)

MVP

0.36

MPC

0.76

ClinPred

0.76

GERP RS

4.1

Varity_R

0.12

gMVP

0.75

Mutation Taster

=56/44

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over