NM_001144877.3:c.1217G>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001144877.3(SCAI):​c.1217G>A​(p.Arg406Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000557 in 1,437,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: SCAI NM_001144877.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3357671).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

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>A	p.Arg406Gln	missense	Exon 13 of 18	NP_001138349.1	Q8N9R8-1
	SCAI	NM_173690.5		c.1286G>A	p.Arg429Gln	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>A	p.Arg406Gln	missense	Exon 13 of 18	ENSP00000336756.6	Q8N9R8-1
	SCAI	ENST00000373549.8	TSL:1	c.1286G>A	p.Arg429Gln	missense	Exon 14 of 19	ENSP00000362650.4	Q8N9R8-2
	SCAI	ENST00000858987.1		c.1199G>A	p.Arg400Gln	missense	Exon 13 of 18	ENSP00000529046.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000125 AC: 3 AN: 240348 AF XY: 0.0000153

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000140

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000557 AC: 8 AN: 1437454 Hom.: 0 Cov.: 26 AF XY: 0.00000977 AC XY: 7 AN XY: 716124

African (AFR) AF: 0.00 AC: 0 AN: 32506

American (AMR) AF: 0.00 AC: 0 AN: 42886

Ashkenazi Jewish (ASJ) AF: 0.0000386 AC: 1 AN: 25914

East Asian (EAS) AF: 0.00 AC: 0 AN: 38812

South Asian (SAS) AF: 0.00 AC: 0 AN: 83892

European-Finnish (FIN) AF: 0.0000939 AC: 5 AN: 53250

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1094958

Other (OTH) AF: 0.00 AC: 0 AN: 59502

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.021	T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	2.0	M
PhyloP100		5.8
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.27
Sift	Benign	0.080	T
Sift4G	Benign	0.095	T
Polyphen		1.0	D
Vest4		0.51
MutPred		0.25		Gain of helix (P = 0.132)
MVP		0.42
MPC		1.8
ClinPred		0.62	D
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.50
Mutation Taster		=57/43	polymorphism

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;