11-65641060-C-G

Variant names:

• chr11-65641060-C-G
• rs763573101
• NM_006747.4:c.139C>G

Variant summary

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

The NM_006747.4(SIPA1):​c.139C>G​(p.Arg47Gly) variant causes a missense 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. 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. R47W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SIPA1 NM_006747.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.157
• Publications: 2 publications found

Genes affected

SIPA1 (HGNC:10885): (signal-induced proliferation-associated 1) The product of this gene is a mitogen induced GTPase activating protein (GAP). It exhibits a specific GAP activity for Ras-related regulatory proteins Rap1 and Rap2, but not for Ran or other small GTPases. This protein may also hamper mitogen-induced cell cycle progression when abnormally or prematurely expressed. It is localized to the perinuclear region. Two alternatively spliced variants encoding the same isoform have been characterized to date. [provided by RefSeq, Jul 2008]

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=0.21169841).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIPA1	NM_006747.4	c.139C>G	p.Arg47Gly	missense_variant	Exon 2 of 16	ENST00000534313.6	NP_006738.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIPA1	ENST00000534313.6	c.139C>G	p.Arg47Gly	missense_variant	Exon 2 of 16	1	NM_006747.4	ENSP00000436269.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	15
DANN	Benign	0.90
DEOGEN2	Benign	0.13	T;.;T;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.76	.;T;T;T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.9	M;.;.;M
PhyloP100		-0.16
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-2.0	N;D;N;N
REVEL	Benign	0.26
Sift	Uncertain	0.011	D;D;D;D
Sift4G	Benign	0.52	T;T;T;T
Polyphen		0.0020	B;.;B;B
Vest4		0.17
MutPred		0.24		Gain of relative solvent accessibility (P = 0.0249);Gain of relative solvent accessibility (P = 0.0249);Gain of relative solvent accessibility (P = 0.0249);Gain of relative solvent accessibility (P = 0.0249);
MVP		0.78
MPC		0.91
ClinPred		0.090	T
GERP RS		2.1
Varity_R		0.14
gMVP		0.49
Mutation Taster		=98/2	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: rs763573101; hg19: chr11-65408531;