9-124971815-G-C

Variant names:

• chr9-124971815-G-C
• rs765417164
• NM_001144877.3:c.1429C>G

Variant summary

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

The NM_001144877.3(SCAI):​c.1429C>G​(p.Leu477Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,394 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. L477F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SCAI NM_001144877.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.79
• Publications: 0 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.1429C>G	p.Leu477Val	missense	Exon 16 of 18	NP_001138349.1	Q8N9R8-1
	SCAI	NM_173690.5		c.1498C>G	p.Leu500Val	missense	Exon 17 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.1429C>G	p.Leu477Val	missense	Exon 16 of 18	ENSP00000336756.6	Q8N9R8-1
	SCAI	ENST00000373549.8	TSL:1	c.1498C>G	p.Leu500Val	missense	Exon 17 of 19	ENSP00000362650.4	Q8N9R8-2
	SCAI	ENST00000858987.1		c.1411C>G	p.Leu471Val	missense	Exon 16 of 18	ENSP00000529046.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453394 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 723288

African (AFR) AF: 0.00 AC: 0 AN: 33090

American (AMR) AF: 0.00 AC: 0 AN: 41490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25878

East Asian (EAS) AF: 0.00 AC: 0 AN: 39484

South Asian (SAS) AF: 0.00 AC: 0 AN: 84422

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109972

Other (OTH) AF: 0.00 AC: 0 AN: 59978

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		8.8
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.28
Sift	Benign	0.034	D
Sift4G	Uncertain	0.049	D
Polyphen		0.98	D
Vest4		0.65
MutPred		0.34		Gain of sheet (P = 0.0049)
MVP		0.37
MPC		0.81
ClinPred		0.95	D
GERP RS		5.1
Varity_R		0.41
gMVP		0.61
Mutation Taster		=41/59	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: rs765417164; hg19: chr9-127734094;