NM_015073.3:c.75C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_015073.3(SIPA1L3):c.75C>T(p.Val25Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00204 in 1,607,620 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 54 hom. )

Consequence

SIPA1L3
NM_015073.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.521

Publications

1 publications found

Variant links:

Genes affected

SIPA1L3 (HGNC:23801): (signal induced proliferation associated 1 like 3) This gene belongs to the signal induced proliferation associated 1 family of genes, which encode GTPase-activating proteins specific for the GTP-binding protein Rap1. Rap1 has been implicated in regulation of cell adhesion, cell polarity, and organization of the cytoskeleton. Like other members of the family, the protein encoded by this gene contains RapGAP and PDZ domains. In addition, this protein contains a C-terminal leucine zipper domain. This gene is proposed to function in epithelial cell morphogenesis and establishment or maintenance of polarity. Consistently, expression of the protein in cell culture showed localization to cell-cell borders in apical regions, and downregulation of the gene in 3D Caco2 cell culture resulted in abnormal cell polarity and morphogenesis. Allelic variants of this gene have been associated with congenital cataracts in humans. [provided by RefSeq, Feb 2016]

SIPA1L3 Gene-Disease associations (from GenCC):

cataract 45
Inheritance: AD, AR, SD, Unknown Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
total early-onset cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SIPA1L3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 19-38081640-C-T is Benign according to our data. Variant chr19-38081640-C-T is described in ClinVar as Benign. ClinVar VariationId is 710484.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.521 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00135 (205/152346) while in subpopulation SAS AF = 0.0203 (98/4834). AF 95% confidence interval is 0.017. There are 3 homozygotes in GnomAd4. There are 126 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AD,Unknown,SD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015073.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIPA1L3	NM_015073.3	MANE Select	c.75C>T	p.Val25Val	synonymous	Exon 3 of 22	NP_055888.1	O60292

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SIPA1L3	ENST00000222345.11	TSL:1 MANE Select	c.75C>T	p.Val25Val	synonymous	Exon 3 of 22	ENSP00000222345.4	O60292
SIPA1L3	ENST00000911499.1		c.75C>T	p.Val25Val	synonymous	Exon 2 of 21	ENSP00000581558.1
SIPA1L3	ENST00000911500.1		c.75C>T	p.Val25Val	synonymous	Exon 3 of 22	ENSP00000581559.1

Frequencies

GnomAD3 genomes

AF:

0.00135

AC:

205

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0200

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00115

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00400

AC:

982

AN:

245230

AF XY:

0.00525

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00125

Gnomad ASJ exome

AF:

0.000912

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000936

Gnomad NFE exome

AF:

0.00152

Gnomad OTH exome

AF:

0.00182

GnomAD4 exome

AF:

0.00211

AC:

3075

AN:

1455274

Hom.:

Cov.:

AF XY:

0.00288

AC XY:

2080

AN XY:

722694

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33356

American (AMR)

AF:

0.00101

AC:

AN:

44586

Ashkenazi Jewish (ASJ)

AF:

0.00111

AC:

AN:

26080

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39512

South Asian (SAS)

AF:

0.0254

AC:

2187

AN:

86124

European-Finnish (FIN)

AF:

0.0000576

AC:

AN:

52078

Middle Eastern (MID)

AF:

0.00722

AC:

AN:

5680

European-Non Finnish (NFE)

AF:

0.000558

AC:

618

AN:

1107876

Other (OTH)

AF:

0.00245

AC:

147

AN:

59982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

191

382

572

763

954

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00135

AC:

205

AN:

152346

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

126

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.0000721

AC:

AN:

41582

American (AMR)

AF:

0.00111

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.0203

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00115

AC:

AN:

68014

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000793

Hom.:

Bravo

AF:

0.000888

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.00196

EpiControl

AF:

0.00225

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

6.3

(source)

DANN

Benign

0.40

PhyloP100

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over