Variant chr11-65641033-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006747.4(SIPA1):c.112C>T(p.Pro38Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SIPA1
NM_006747.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.402

Variant links:

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]

SIPA1 links:

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ACMG classification

Classification made for transcript

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=0.16678125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIPA1	NM_006747.4 linkuse as main transcript	c.112C>T	p.Pro38Ser	missense_variant	2/16	ENST00000534313.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SIPA1	ENST00000534313.6 linkuse as main transcript	c.112C>T	p.Pro38Ser	missense_variant	2/16	1	NM_006747.4	P1
SIPA1	ENST00000394224.3 linkuse as main transcript	c.112C>T	p.Pro38Ser	missense_variant	2/16	1		P1
SIPA1	ENST00000527525.5 linkuse as main transcript	c.112C>T	p.Pro38Ser	missense_variant	2/17	2
SIPA1	ENST00000533361.1 linkuse as main transcript	c.112C>T	p.Pro38Ser	missense_variant	3/3	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000491

AC:

AN:

203708

Hom.:

AF XY:

0.00

AC XY:

AN XY:

113016

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000113

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1440464

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715990

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 03, 2023

The c.112C>T (p.P38S) alteration is located in exon 2 (coding exon 1) of the SIPA1 gene. This alteration results from a C to T substitution at nucleotide position 112, causing the proline (P) at amino acid position 38 to be replaced by a serine (S). 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

0.097

BayesDel_addAF

Benign

-0.015

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;.;T;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.72

.;T;T;T

M_CAP

Pathogenic

0.52

MetaRNN

Benign

0.17

T;T;T;T

MetaSVM

Benign

-0.55

MutationAssessor

Benign

1.6

L;.;.;L

MutationTaster

Benign

0.53

N;N;N;N

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-2.0

N;D;N;N

REVEL

Benign

0.22

Sift

Benign

0.19

T;T;T;T

Sift4G

Benign

0.29

T;T;T;T

Polyphen

0.26

B;.;B;B

Vest4

0.10

MutPred

0.065

Gain of MoRF binding (P = 0.0532);Gain of MoRF binding (P = 0.0532);Gain of MoRF binding (P = 0.0532);Gain of MoRF binding (P = 0.0532);

MVP

0.75

MPC

0.79

ClinPred

0.19

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.082

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over