Variant chr11-65641087-G-A 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.166G>A(p.Asp56Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000513 in 1,599,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

SIPA1
NM_006747.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.13

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:

Genome browser will be placed here

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=0.24446023).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIPA1	NM_006747.4 linkuse as main transcript	c.166G>A	p.Asp56Asn	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.166G>A	p.Asp56Asn	missense_variant	2/16	1	NM_006747.4	P1
SIPA1	ENST00000394224.3 linkuse as main transcript	c.166G>A	p.Asp56Asn	missense_variant	2/16	1		P1
SIPA1	ENST00000527525.5 linkuse as main transcript	c.166G>A	p.Asp56Asn	missense_variant	2/17	2
SIPA1	ENST00000533361.1 linkuse as main transcript	c.166G>A	p.Asp56Asn	missense_variant	3/3	4

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000585

AC:

AN:

222134

Hom.:

AF XY:

0.0000728

AC XY:

AN XY:

123584

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:

0.0000333

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000532

AC:

AN:

1447600

Hom.:

Cov.:

AF XY:

0.0000625

AC XY:

AN XY:

720268

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000622

Gnomad4 OTH exome

AF:

0.0000500

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000607

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000423

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jun 04, 2024

The c.166G>A (p.D56N) alteration is located in exon 2 (coding exon 1) of the SIPA1 gene. This alteration results from a G to A substitution at nucleotide position 166, causing the aspartic acid (D) at amino acid position 56 to be replaced by an asparagine (N). 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

0.29

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;.;T;T

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.85

.;T;T;T

M_CAP

Pathogenic

0.49

MetaRNN

Benign

0.24

T;T;T;T

MetaSVM

Benign

-0.32

MutationAssessor

Benign

1.8

L;.;.;L

MutationTaster

Benign

0.63

N;N;N;N

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-1.2

N;D;N;N

REVEL

Benign

0.27

Sift

Benign

0.14

T;T;T;T

Sift4G

Benign

0.27

T;D;T;T

Polyphen

0.70

P;.;P;P

Vest4

0.21

MutPred

0.10

Gain of MoRF binding (P = 0.0413);Gain of MoRF binding (P = 0.0413);Gain of MoRF binding (P = 0.0413);Gain of MoRF binding (P = 0.0413);

MVP

0.86

MPC

0.87

ClinPred

0.090

GERP RS

5.4

Varity_R

0.11

gMVP

0.32

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

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