rs749443708

Variant names:

• chr11-65641025-C-G
• rs749443708
• NM_006747.4:c.104C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-65641025-C-G
• chr11-65641025-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006747.4(SIPA1):​c.104C>G​(p.Pro35Arg) 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SIPA1 NM_006747.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34883088).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIPA1	NM_006747.4	c.104C>G	p.Pro35Arg	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.104C>G	p.Pro35Arg	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

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;.;T;T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.78	.;T;T;T
M_CAP	Pathogenic	0.57	D
MetaRNN	Benign	0.35	T;T;T;T
MetaSVM	Uncertain	0.023	D
MutationAssessor	Uncertain	2.2	M;.;.;M
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-2.1	N;D;N;N
REVEL	Uncertain	0.29
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		0.97	D;.;D;D
Vest4		0.28
MutPred		0.16		Gain of MoRF binding (P = 0.0031);Gain of MoRF binding (P = 0.0031);Gain of MoRF binding (P = 0.0031);Gain of MoRF binding (P = 0.0031);
MVP		0.86
MPC		1.7
ClinPred		0.94	D
GERP RS		5.3
Varity_R		0.15
gMVP		0.48

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: rs749443708; hg19: chr11-65408496;