Variant 11-65641132-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006747.4(SIPA1):c.211C>T(p.Arg71Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000561 in 1,603,384 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SIPA1
NM_006747.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.175

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIPA1	NM_006747.4 linkuse as main transcript	c.211C>T	p.Arg71Cys	missense_variant	2/16	ENST00000534313.6	NP_006738.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SIPA1	ENST00000534313.6 linkuse as main transcript	c.211C>T	p.Arg71Cys	missense_variant	2/16	1	NM_006747.4	ENSP00000436269	P1
SIPA1	ENST00000394224.3 linkuse as main transcript	c.211C>T	p.Arg71Cys	missense_variant	2/16	1		ENSP00000377771	P1
SIPA1	ENST00000527525.5 linkuse as main transcript	c.211C>T	p.Arg71Cys	missense_variant	2/17	2		ENSP00000433686
SIPA1	ENST00000533361.1 linkuse as main transcript	c.211C>T	p.Arg71Cys	missense_variant	3/3	4		ENSP00000436683

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000852

AC:

AN:

234864

Hom.:

AF XY:

0.00000772

AC XY:

AN XY:

129546

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000562

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

AF:

0.00000482

AC:

AN:

1451020

Hom.:

Cov.:

AF XY:

0.00000554

AC XY:

AN XY:

722252

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152364

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000166

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Jan 19, 2022

The c.211C>T (p.R71C) 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 211, causing the arginine (R) at amino acid position 71 to be replaced by a cysteine (C). 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

Pathogenic

0.57

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

T;.;T;T

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Benign

0.50

LIST_S2

Uncertain

0.90

.;D;D;D

M_CAP

Pathogenic

0.78

MetaRNN

Uncertain

0.49

T;T;T;T

MetaSVM

Uncertain

-0.17

MutationAssessor

Benign

1.8

L;.;.;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.93

PROVEAN

Uncertain

-3.4

D;D;D;D

REVEL

Uncertain

0.46

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Uncertain

0.0090

D;D;D;D

Polyphen

1.0

D;.;D;D

Vest4

0.45

MVP

0.88

MPC

1.9

ClinPred

0.83

GERP RS

4.5

Varity_R

0.23

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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