9-124971793-A-G

Position:

• chr9-124971793-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001144877.3(SCAI):​c.1451T>C​(p.Met484Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,458,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: SCAI NM_001144877.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.20

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.20648244).
• BS2: High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAI	NM_001144877.3	c.1451T>C	p.Met484Thr	missense_variant	16/18	ENST00000336505.11	NP_001138349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCAI	ENST00000336505.11	c.1451T>C	p.Met484Thr	missense_variant	16/18	1	NM_001144877.3	ENSP00000336756.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000117 AC: 17 AN: 1458976 Hom.: 0 Cov.: 30 AF XY: 0.00000827 AC XY: 6 AN XY: 725946

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: 0.0000144

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 21, 2024

The c.1520T>C (p.M507T) alteration is located in exon 17 (coding exon 17) of the SCAI gene. This alteration results from a T to C substitution at nucleotide position 1520, causing the methionine (M) at amino acid position 507 to be replaced by a threonine (T). 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	0.24
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	21
DANN	Benign	0.81
DEOGEN2	Benign	0.0044	T;.
Eigen	Benign	-0.092
Eigen_PC	Benign	0.12
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	0.78	N;N
REVEL	Benign	0.27
Sift	Benign	1.0	T;T
Sift4G	Benign	0.93	T;T
Polyphen		0.37	B;B
Vest4		0.61
MutPred		0.43		Gain of loop (P = 0.0166);.;
MVP		0.16
MPC		0.84
ClinPred		0.79	D
GERP RS		5.1
Varity_R		0.24
gMVP		0.67

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

LitVar

Other links and lift over

dbSNP: rs1831664548; hg19: chr9-127734072; COSMIC: COSV57175901; COSMIC: COSV57175901;