Variant 9-125003487-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001144877.3(SCAI):c.945G>C(p.Met315Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SCAI
NM_001144877.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.94

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:

SCAI (HGNC:):

SCAI links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12279099).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAI	NM_001144877.3 linkuse as main transcript	c.945G>C	p.Met315Ile	missense_variant	10/18	ENST00000336505.11	NP_001138349.1	Q8N9R8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SCAI	ENST00000336505.11 linkuse as main transcript	c.945G>C	p.Met315Ile	missense_variant	10/18	1	NM_001144877.3	ENSP00000336756.6	Q8N9R8-1
SCAI	ENST00000373549.8 linkuse as main transcript	c.1014G>C	p.Met338Ile	missense_variant	11/19	1		ENSP00000362650.4	Q8N9R8-2
SCAI	ENST00000477186.5 linkuse as main transcript	n.945G>C		non_coding_transcript_exon_variant	10/18	2		ENSP00000419576.1	Q3SXZ0
SCAI	ENST00000487795.1 linkuse as main transcript	n.204G>C		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458558

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725824

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

The c.1014G>C (p.M338I) alteration is located in exon 11 (coding exon 11) of the SCAI gene. This alteration results from a G to C substitution at nucleotide position 1014, causing the methionine (M) at amino acid position 338 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0051

T;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.0050

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.55

N;.

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.85

N;N

REVEL

Benign

0.051

Sift

Benign

0.34

T;T

Sift4G

Benign

0.44

T;T

Polyphen

0.069

B;B

Vest4

0.34

MutPred

0.19

Loss of disorder (P = 0.0739);.;

MVP

0.13

MPC

0.81

ClinPred

0.51

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.31

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over