9-124999918-C-A

Variant names:

• chr9-124999918-C-A
• rs747158707
• NM_001144877.3:c.1217G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001144877.3(SCAI):​c.1217G>T​(p.Arg406Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R406Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SCAI NM_001144877.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.83
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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.1217G>T	p.Arg406Leu	missense	Exon 13 of 18	NP_001138349.1	Q8N9R8-1
	SCAI	NM_173690.5		c.1286G>T	p.Arg429Leu	missense	Exon 14 of 19	NP_775961.2	Q8N9R8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAI	ENST00000336505.11	TSL:1 MANE Select	c.1217G>T	p.Arg406Leu	missense	Exon 13 of 18	ENSP00000336756.6	Q8N9R8-1
	SCAI	ENST00000373549.8	TSL:1	c.1286G>T	p.Arg429Leu	missense	Exon 14 of 19	ENSP00000362650.4	Q8N9R8-2
	SCAI	ENST00000858987.1		c.1199G>T	p.Arg400Leu	missense	Exon 13 of 18	ENSP00000529046.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	2.0	M
PhyloP100		5.8
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.28
Sift	Benign	0.17	T
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.71
MutPred		0.26		Gain of helix (P = 0.0199)
MVP		0.35
MPC		1.7
ClinPred		0.90	D
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.34
gMVP		0.61
Mutation Taster		=24/76	disease causing

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

Other links and lift over

dbSNP: rs747158707; hg19: chr9-127762197;