rs200091326

Variant names:

• chr12-113102007-C-A
• rs200091326
• NM_001301202.2:c.2107G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-113102007-C-A
• chr12-113102007-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001301202.2(RASAL1):​c.2107G>T​(p.Ala703Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. A703T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RASAL1 NM_001301202.2 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209

Genes affected

RASAL1 (HGNC:9873): (RAS protein activator like 1) The protein encoded by this gene is member of the GAP1 family of GTPase-activating proteins. These proteins stimulate the GTPase activity of normal RAS p21 but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, thereby allowing control of cellular proliferation and differentiation. This particular family member contains domains which are characteristic of the GAP1 subfamily of RasGAP proteins but, in contrast to the other GAP1 family members, this protein is strongly and selectively expressed in endocrine tissues. Alternatively spliced transcript variants that encode different isoforms have been described [provided by RefSeq, Jul 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=0.14400485).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASAL1	NM_001301202.2	c.2107G>T	p.Ala703Ser	missense_variant, splice_region_variant	Exon 19 of 21	ENST00000548055.2	NP_001288131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASAL1	ENST00000548055.2	c.2107G>T	p.Ala703Ser	missense_variant, splice_region_variant	Exon 19 of 21	1	NM_001301202.2	ENSP00000448510.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460184 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726402

Gnomad4 AFR exome AF: 0.00

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: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	4.7
DANN	Benign	0.82
DEOGEN2	Benign	0.15	.;T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.63	T;T;T;T
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	0.43	.;N;.;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.38	N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.45	T;T;T;T
Sift4G	Benign	0.74	T;T;T;T
Polyphen		0.0030, 0.0040	.;B;B;.
Vest4		0.13
MutPred		0.33		.;Gain of glycosylation at A702 (P = 0.0163);.;.;
MVP		0.73
MPC		0.21
ClinPred		0.031	T
GERP RS		0.61
Varity_R		0.050
gMVP		0.21

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

LitVar

Other links and lift over

dbSNP: rs200091326; hg19: chr12-113539812;