rs200979758

Variant names:

• chr9-124952890-G-A
• rs200979758
• NM_001144877.3:c.1738C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-124952890-G-A
• chr9-124952890-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001144877.3(SCAI):​c.1738C>T​(p.His580Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,459,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H580N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SCAI NM_001144877.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.56
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2023302).

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.1738C>T	p.His580Tyr	missense	Exon 18 of 18	NP_001138349.1	Q8N9R8-1
	SCAI	NM_173690.5		c.1807C>T	p.His603Tyr	missense	Exon 19 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.1738C>T	p.His580Tyr	missense	Exon 18 of 18	ENSP00000336756.6	Q8N9R8-1
	SCAI	ENST00000373549.8	TSL:1	c.1807C>T	p.His603Tyr	missense	Exon 19 of 19	ENSP00000362650.4	Q8N9R8-2
	SCAI	ENST00000858987.1		c.1720C>T	p.His574Tyr	missense	Exon 18 of 18	ENSP00000529046.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1459116 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726076

African (AFR) AF: 0.0000299 AC: 1 AN: 33414

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39634

South Asian (SAS) AF: 0.00 AC: 0 AN: 86208

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109562

Other (OTH) AF: 0.00 AC: 0 AN: 60292

GnomAD4 genome Cov.: 32

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	0.074
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0050	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.69	N
PhyloP100		4.6
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.091
Sift	Benign	0.12	T
Sift4G	Uncertain	0.045	D
Polyphen		0.85	P
Vest4		0.46
MutPred		0.26		Gain of helix (P = 0.0325)
MVP		0.093
MPC		1.2
ClinPred		0.56	D
GERP RS		5.2
Varity_R		0.17
gMVP		0.41
Mutation Taster		=85/15	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: rs200979758; hg19: chr9-127715169;