Genetic Variant SCAI:p.Ser393Gly (chr9-124999958-T-C) – 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_001144877.3(SCAI):c.1177A>G(p.Ser393Gly) variant causes a missense change involving the alteration of a 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: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SCAI
NM_001144877.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67

Publications

0 publications found

Variant links:

Genes affected

SCAI (HGNC:26709): (suppressor of cancer cell invasion) This gene encodes a regulator of cell migration. The encoded protein appears to function in the RhoA (ras homolog gene family, member A)-Dia1 (diaphanous homolog 1) signal transduction pathway. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]

SCAI 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=0.294762).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144877.3. 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
	SCAI	NM_001144877.3	MANE Select	c.1177A>G	p.Ser393Gly	missense	Exon 13 of 18	NP_001138349.1	Q8N9R8-1
	SCAI	NM_173690.5		c.1246A>G	p.Ser416Gly	missense	Exon 14 of 19	NP_775961.2	Q8N9R8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCAI	ENST00000336505.11	TSL:1 MANE Select	c.1177A>G	p.Ser393Gly	missense	Exon 13 of 18	ENSP00000336756.6	Q8N9R8-1
SCAI	ENST00000373549.8	TSL:1	c.1246A>G	p.Ser416Gly	missense	Exon 14 of 19	ENSP00000362650.4	Q8N9R8-2
SCAI	ENST00000858987.1		c.1159A>G	p.Ser387Gly	missense	Exon 13 of 18	ENSP00000529046.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1438546

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716070

African (AFR)

AF:

0.00

AC:

AN:

32336

American (AMR)

AF:

0.00

AC:

AN:

41442

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25836

East Asian (EAS)

AF:

0.00

AC:

AN:

38876

South Asian (SAS)

AF:

0.00

AC:

AN:

82618

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53060

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1099124

Other (OTH)

AF:

0.00

AC:

AN:

59532

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

0.087

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.014

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.2

PhyloP100

7.7

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-2.2

REVEL

Benign

0.17

Sift

Benign

0.26

Sift4G

Benign

0.26

Polyphen

0.63

Vest4

0.33

MutPred

0.26

Loss of catalytic residue at S393 (P = 0.0191)

MVP

0.19

MPC

1.1

ClinPred

0.96

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.35

gMVP

0.40

Mutation Taster

=62/38

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