Variant 1-232428542-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_020808.5(SIPA1L2):c.4279A>C(p.Met1427Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00767 in 1,585,292 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0057 ( 5 hom., cov: 31)

Exomes 𝑓: 0.0079 ( 67 hom. )

Consequence

SIPA1L2
NM_020808.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0920

Variant links:

Genes affected

SIPA1L2 (HGNC:23800): (signal induced proliferation associated 1 like 2) This gene encodes a member of the signal-induced proliferation-associated 1 like family. Members of this family contain a GTPase activating domain, a PDZ domain and a C-terminal coiled-coil domain with a leucine zipper. A similar protein in rat acts as a GTPases for the small GTPase Rap. [provided by RefSeq, Sep 2015]

SIPA1L2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005518347).

BP6

Variant 1-232428542-T-G is Benign according to our data. Variant chr1-232428542-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2640082.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIPA1L2	NM_020808.5 linkuse as main transcript	c.4279A>C	p.Met1427Leu	missense_variant	17/23	ENST00000674635.1	NP_065859.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIPA1L2	ENST00000674635.1 linkuse as main transcript	c.4279A>C	p.Met1427Leu	missense_variant	17/23		NM_020808.5	ENSP00000502693	A1	Q9P2F8-1

Frequencies

GnomAD3 genomes

AF:

0.00572

AC:

870

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00583

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00557

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00932

Gnomad OTH

AF:

0.00576

GnomAD3 exomes

AF:

0.00580

AC:

1297

AN:

223572

Hom.:

AF XY:

0.00579

AC XY:

704

AN XY:

121592

show subpopulations

Gnomad AFR exome

AF:

0.00106

Gnomad AMR exome

AF:

0.00352

Gnomad ASJ exome

AF:

0.00165

Gnomad EAS exome

AF:

0.000126

Gnomad SAS exome

AF:

0.00134

Gnomad FIN exome

AF:

0.00779

Gnomad NFE exome

AF:

0.00881

Gnomad OTH exome

AF:

0.00803

GnomAD4 exome

AF:

0.00788

AC:

11296

AN:

1433150

Hom.:

Cov.:

AF XY:

0.00779

AC XY:

5547

AN XY:

712206

show subpopulations

Gnomad4 AFR exome

AF:

0.00145

Gnomad4 AMR exome

AF:

0.00344

Gnomad4 ASJ exome

AF:

0.00166

Gnomad4 EAS exome

AF:

0.0000522

Gnomad4 SAS exome

AF:

0.00145

Gnomad4 FIN exome

AF:

0.00742

Gnomad4 NFE exome

AF:

0.00918

Gnomad4 OTH exome

AF:

0.00759

GnomAD4 genome

AF:

0.00571

AC:

869

AN:

152142

Hom.:

Cov.:

AF XY:

0.00544

AC XY:

405

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.00582

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00250

Gnomad4 FIN

AF:

0.00557

Gnomad4 NFE

AF:

0.00931

Gnomad4 OTH

AF:

0.00570

Alfa

AF:

0.00769

Hom.:

Bravo

AF:

0.00511

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00908

AC:

ESP6500AA

AF:

0.00361

AC:

ESP6500EA

AF:

0.00880

AC:

ExAC

AF:

0.00515

AC:

623

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

SIPA1L2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.6

DANN

Benign

0.38

DEOGEN2

Benign

0.017

T;T;.

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.59

.;T;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.0055

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

N;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.64

N;N;N

REVEL

Benign

0.074

Sift

Benign

0.31

T;T;T

Sift4G

Benign

0.40

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.085

MutPred

0.24

Loss of disorder (P = 0.0664);Loss of disorder (P = 0.0664);.;

MVP

0.068

MPC

0.16

ClinPred

0.0027

GERP RS

-2.9

Varity_R

0.078

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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