Variant 1-232432400-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_020808.5(SIPA1L2):c.4103T>G(p.Val1368Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000748 in 1,614,114 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00077 ( 2 hom. )

Consequence

SIPA1L2
NM_020808.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.82

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 Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10330132).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIPA1L2	NM_020808.5 linkuse as main transcript	c.4103T>G	p.Val1368Gly	missense_variant	16/23	ENST00000674635.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIPA1L2	ENST00000674635.1 linkuse as main transcript	c.4103T>G	p.Val1368Gly	missense_variant	16/23		NM_020808.5	A1	Q9P2F8-1

Frequencies

GnomAD3 genomes

AF:

0.000493

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000955

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000409

AC:

102

AN:

249576

Hom.:

AF XY:

0.000377

AC XY:

AN XY:

135406

show subpopulations

Gnomad AFR exome

AF:

0.000258

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.000803

Gnomad OTH exome

AF:

0.000660

GnomAD4 exome

AF:

0.000774

AC:

1132

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000767

AC XY:

558

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.000970

Gnomad4 OTH exome

AF:

0.000646

GnomAD4 genome

AF:

0.000493

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000955

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000761

Hom.:

Bravo

AF:

0.000514

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00120

AC:

ExAC

AF:

0.000364

AC:

EpiCase

AF:

0.000818

EpiControl

AF:

0.000889

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

Dec 16, 2023

The c.4103T>G (p.V1368G) alteration is located in exon 14 (coding exon 14) of the SIPA1L2 gene. This alteration results from a T to G substitution at nucleotide position 4103, causing the valine (V) at amino acid position 1368 to be replaced by a glycine (G). 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

0.31

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Uncertain

0.040

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.043

T;T;.

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.99

M_CAP

Uncertain

0.097

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Uncertain

-0.21

MutationAssessor

Uncertain

2.1

M;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.80

N;N;N

REVEL

Benign

0.21

Sift

Uncertain

0.027

D;D;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

0.92

P;P;D

Vest4

0.46

MVP

0.17

MPC

0.77

ClinPred

0.029

GERP RS

5.9

Varity_R

0.18

gMVP

0.69

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