9-124952890-G-A

Position:

• chr9-124952890-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAI	NM_001144877.3	c.1738C>T	p.His580Tyr	missense_variant	18/18	ENST00000336505.11	NP_001138349.1
SCAI	NM_173690.5	c.1807C>T	p.His603Tyr	missense_variant	19/19		NP_775961.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCAI	ENST00000336505.11	c.1738C>T	p.His580Tyr	missense_variant	18/18	1	NM_001144877.3	ENSP00000336756.6

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

Gnomad4 AFR exome AF: 0.0000299

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: 0.0000187

Gnomad4 NFE exome AF: 9.01e-7

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

Nov 10, 2024

The c.1807C>T (p.H603Y) alteration is located in exon 19 (coding exon 19) of the SCAI gene. This alteration results from a C to T substitution at nucleotide position 1807, causing the histidine (H) at amino acid position 603 to be replaced by a tyrosine (Y). 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	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;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.81	N;N
REVEL	Benign	0.091
Sift	Benign	0.12	T;T
Sift4G	Uncertain	0.045	D;D
Polyphen		0.85	P;B
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

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: chr9-127715169;