9-125020760-C-A

Position:

• chr9-125020760-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001144877.3(SCAI):​c.522G>T​(p.Leu174Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000783 in 1,277,500 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: SCAI NM_001144877.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.343

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAI	NM_001144877.3	c.522G>T	p.Leu174Phe	missense_variant	7/18	ENST00000336505.11	NP_001138349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCAI	ENST00000336505.11	c.522G>T	p.Leu174Phe	missense_variant	7/18	1	NM_001144877.3	ENSP00000336756.6
SCAI	ENST00000373549.8	c.591G>T	p.Leu197Phe	missense_variant	8/19	1		ENSP00000362650.4
SCAI	ENST00000477186.5	n.522G>T		non_coding_transcript_exon_variant	7/18	2		ENSP00000419576.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.83e-7 AC: 1 AN: 1277500 Hom.: 0 Cov.: 18 AF XY: 0.00000156 AC XY: 1 AN XY: 642688

Gnomad4 AFR exome AF: 0.0000361

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Feb 22, 2023

The c.591G>T (p.L197F) alteration is located in exon 8 (coding exon 8) of the SCAI gene. This alteration results from a G to T substitution at nucleotide position 591, causing the leucine (L) at amino acid position 197 to be replaced by a phenylalanine (F). 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	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;.
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.075	D
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.1	D;D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.019	D;D
Polyphen		1.0	D;D
Vest4		0.79
MutPred		0.26		Gain of loop (P = 0.069);.;
MVP		0.46
MPC		1.7
ClinPred		0.98	D
GERP RS		0.43
Varity_R		0.35
gMVP		0.44

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.

Other links and lift over

hg19: chr9-127783039;