Variant 14-71588038-C-A 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_001386936.1(SIPA1L1):c.166C>A(p.Pro56Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0111 in 1,613,896 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0076 ( 6 hom., cov: 32)

Exomes 𝑓: 0.011 ( 111 hom. )

Consequence

SIPA1L1
NM_001386936.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.98

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050117075).

BP6

Variant 14-71588038-C-A is Benign according to our data. Variant chr14-71588038-C-A is described in ClinVar as [Benign]. Clinvar id is 773722.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIPA1L1	NM_001386936.1 linkuse as main transcript	c.166C>A	p.Pro56Thr	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.166C>A	p.Pro56Thr	missense_variant	5/24	1	NM_001386936.1	ENSP00000370630	P4	O43166-2
SIPA1L1	ENST00000555818.5 linkuse as main transcript	c.166C>A	p.Pro56Thr	missense_variant	2/22	1		ENSP00000450832		O43166-1
	ENST00000647653.1 linkuse as main transcript	n.1324G>T		non_coding_transcript_exon_variant	2/2
SIPA1L1	ENST00000358550.6 linkuse as main transcript	c.166C>A	p.Pro56Thr	missense_variant	2/21	2		ENSP00000351352	A1	O43166-3

Frequencies

GnomAD3 genomes

AF:

0.00765

AC:

1163

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00258

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.00354

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.0126

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0122

Gnomad OTH

AF:

0.00624

GnomAD3 exomes

AF:

0.00791

AC:

1981

AN:

250498

Hom.:

AF XY:

0.00776

AC XY:

1052

AN XY:

135490

show subpopulations

Gnomad AFR exome

AF:

0.00235

Gnomad AMR exome

AF:

0.00255

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00275

Gnomad FIN exome

AF:

0.0114

Gnomad NFE exome

AF:

0.0129

Gnomad OTH exome

AF:

0.00884

GnomAD4 exome

AF:

0.0115

AC:

16796

AN:

1461738

Hom.:

111

Cov.:

AF XY:

0.0111

AC XY:

8066

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.00185

Gnomad4 AMR exome

AF:

0.00291

Gnomad4 ASJ exome

AF:

0.000421

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00335

Gnomad4 FIN exome

AF:

0.0117

Gnomad4 NFE exome

AF:

0.0136

Gnomad4 OTH exome

AF:

0.00843

GnomAD4 genome

AF:

0.00764

AC:

1163

AN:

152158

Hom.:

Cov.:

AF XY:

0.00777

AC XY:

578

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00258

Gnomad4 AMR

AF:

0.00353

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00374

Gnomad4 FIN

AF:

0.0126

Gnomad4 NFE

AF:

0.0122

Gnomad4 OTH

AF:

0.00618

Alfa

AF:

0.0102

Hom.:

Bravo

AF:

0.00680

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.0140

AC:

ESP6500AA

AF:

0.00409

AC:

ESP6500EA

AF:

0.0110

AC:

ExAC

AF:

0.00745

AC:

905

Asia WGS

AF:

0.00144

AC:

AN:

3476

EpiCase

AF:

0.0112

EpiControl

AF:

0.0114

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.049

.;T;.

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.91

D;D;D

MetaRNN

Benign

0.0050

T;T;T

MetaSVM

Benign

-0.50

MutationAssessor

Benign

1.8

L;L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.5

N;N;N

REVEL

Uncertain

0.38

Sift

Benign

0.046

D;T;D

Sift4G

Uncertain

0.041

D;D;D

Polyphen

0.011

B;P;.

Vest4

0.40

MVP

0.43

MPC

0.47

ClinPred

0.0080

GERP RS

5.5

Varity_R

0.076

gMVP

0.41

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