Variant 14-71588045-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001386936.1(SIPA1L1):c.173G>A(p.Arg58Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SIPA1L1
NM_001386936.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.00

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:

ENSG00000285612 (HGNC:):

ENSG00000285612 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3072031).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIPA1L1	NM_001386936.1 linkuse as main transcript	c.173G>A	p.Arg58Gln	missense_variant	5/24	ENST00000381232.8	NP_001373865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SIPA1L1	ENST00000381232.8 linkuse as main transcript	c.173G>A	p.Arg58Gln	missense_variant	5/24	1	NM_001386936.1	ENSP00000370630.3	O43166-2
SIPA1L1	ENST00000555818.5 linkuse as main transcript	c.173G>A	p.Arg58Gln	missense_variant	2/22	1		ENSP00000450832.1	O43166-1
SIPA1L1	ENST00000358550.6 linkuse as main transcript	c.173G>A	p.Arg58Gln	missense_variant	2/21	2		ENSP00000351352.2	O43166-3
ENSG00000285612	ENST00000647653.1 linkuse as main transcript	n.1317C>T		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461766

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Sep 05, 2024

The c.173G>A (p.R58Q) alteration is located in exon 2 (coding exon 1) of the SIPA1L1 gene. This alteration results from a G to A substitution at nucleotide position 173, causing the arginine (R) at amino acid position 58 to be replaced by a glutamine (Q). 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

0.15

BayesDel_addAF

Uncertain

0.096

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

.;T;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Benign

0.036

MetaRNN

Benign

0.31

T;T;T

MetaSVM

Benign

-0.30

MutationAssessor

Uncertain

2.0

M;M;M

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.62

N;N;N

REVEL

Benign

0.26

Sift

Benign

0.29

T;T;T

Sift4G

Benign

0.55

T;T;T

Polyphen

0.97

D;D;.

Vest4

0.44

MutPred

0.084

Loss of glycosylation at P57 (P = 0.0812);Loss of glycosylation at P57 (P = 0.0812);Loss of glycosylation at P57 (P = 0.0812);

MVP

0.75

MPC

1.1

ClinPred

0.88

GERP RS

5.5

Varity_R

0.066

gMVP

0.43

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