Variant chr14-71587991-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001386936.1(SIPA1L1):c.119G>A(p.Arg40Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0096 in 1,614,038 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0078 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0098 ( 91 hom. )

Consequence

SIPA1L1
NM_001386936.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 8.02

Variant links:

Genes affected

SIPA1L1 (HGNC:20284): (signal induced proliferation associated 1 like 1) Predicted to enable GTPase activator activity; actin filament binding activity; and protein kinase binding activity. Predicted to be involved in several processes, including actin cytoskeleton organization; activation of GTPase activity; and regulation of postsynapse organization. Located in actin cytoskeleton and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SIPA1L1 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007160008).

BP6

Variant 14-71587991-G-A is Benign according to our data. Variant chr14-71587991-G-A is described in ClinVar as [Benign]. Clinvar id is 783046.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIPA1L1	NM_001386936.1 linkuse as main transcript	c.119G>A	p.Arg40Gln	missense_variant	5/24	ENST00000381232.8	NP_001373865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIPA1L1	ENST00000381232.8 linkuse as main transcript	c.119G>A	p.Arg40Gln	missense_variant	5/24	1	NM_001386936.1	ENSP00000370630	P4	O43166-2
	ENST00000647653.1 linkuse as main transcript	n.1371C>T		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.00784

AC:

1193

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.0471

Gnomad AMR

AF:

0.00563

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.0108

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0123

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00763

AC:

1917

AN:

251128

Hom.:

AF XY:

0.00791

AC XY:

1073

AN XY:

135708

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00283

Gnomad ASJ exome

AF:

0.00467

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00392

Gnomad FIN exome

AF:

0.0112

Gnomad NFE exome

AF:

0.0118

Gnomad OTH exome

AF:

0.00734

GnomAD4 exome

AF:

0.00979

AC:

14305

AN:

1461802

Hom.:

Cov.:

AF XY:

0.00969

AC XY:

7046

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00137

Gnomad4 AMR exome

AF:

0.00284

Gnomad4 ASJ exome

AF:

0.00494

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00413

Gnomad4 FIN exome

AF:

0.0101

Gnomad4 NFE exome

AF:

0.0113

Gnomad4 OTH exome

AF:

0.00843

GnomAD4 genome

AF:

0.00784

AC:

1193

AN:

152236

Hom.:

Cov.:

AF XY:

0.00736

AC XY:

548

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00562

Gnomad4 ASJ

AF:

0.00433

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.0108

Gnomad4 NFE

AF:

0.0123

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.0108

Hom.:

Bravo

AF:

0.00655

TwinsUK

AF:

0.00998

AC:

ALSPAC

AF:

0.0104

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.0108

AC:

ExAC

AF:

0.00826

AC:

1003

Asia WGS

AF:

0.00231

AC:

AN:

3476

EpiCase

AF:

0.0139

EpiControl

AF:

0.0115

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.035

.;T;.

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

D;D;D

MetaRNN

Benign

0.0072

T;T;T

MetaSVM

Uncertain

-0.25

MutationAssessor

Benign

1.6

L;L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.80

N;N;N

REVEL

Uncertain

0.37

Sift

Benign

0.28

T;T;T

Sift4G

Benign

0.30

T;T;T

Polyphen

0.94

P;D;.

Vest4

0.54

MVP

0.78

MPC

0.66

ClinPred

0.036

GERP RS

5.5

Varity_R

0.20

gMVP

0.51

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