Genetic Variant INPPL1:p.Ser329Ser (chr11-72230168-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001567.4(INPPL1):c.987A>G(p.Ser329Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,610,878 control chromosomes in the GnomAD database, including 39,762 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 7134 hom., cov: 33)

Exomes 𝑓: 0.20 ( 32628 hom. )

Consequence

INPPL1
NM_001567.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.77

Publications

31 publications found

Variant links:

Genes affected

INPPL1 (HGNC:6080): (inositol polyphosphate phosphatase like 1) The protein encoded by this gene is an SH2-containing 5'-inositol phosphatase that is involved in the regulation of insulin function. The encoded protein also plays a role in the regulation of epidermal growth factor receptor turnover and actin remodelling. Additionally, this gene supports metastatic growth in breast cancer and is a valuable biomarker for breast cancer. [provided by RefSeq, Jan 2009]

INPPL1 Gene-Disease associations (from GenCC):

opsismodysplasia
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
schneckenbecken dysplasia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

INPPL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 11-72230168-A-G is Benign according to our data. Variant chr11-72230168-A-G is described in ClinVar as Benign. ClinVar VariationId is 1170422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.77 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001567.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
INPPL1	NM_001567.4	MANE Select	c.987A>G	p.Ser329Ser	synonymous	Exon 9 of 28	NP_001558.3
INPPL1	NM_001440434.1		c.1053A>G	p.Ser351Ser	synonymous	Exon 9 of 28	NP_001427363.1
INPPL1	NM_001440435.1		c.987A>G	p.Ser329Ser	synonymous	Exon 10 of 29	NP_001427364.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
INPPL1	ENST00000298229.7	TSL:1 MANE Select	c.987A>G	p.Ser329Ser	synonymous	Exon 9 of 28	ENSP00000298229.2
INPPL1	ENST00000538751.5	TSL:1	c.261A>G	p.Ser87Ser	synonymous	Exon 8 of 27	ENSP00000444619.1
INPPL1	ENST00000540329.5	TSL:3	c.171A>G	p.Ser57Ser	synonymous	Exon 6 of 7	ENSP00000440018.1

Frequencies

GnomAD3 genomes

AF:

0.276

AC:

41943

AN:

152140

Hom.:

7131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.477

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.175

Gnomad EAS

AF:

0.336

Gnomad SAS

AF:

0.359

Gnomad FIN

AF:

0.210

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.170

Gnomad OTH

AF:

0.234

GnomAD2 exomes

AF:

0.243

AC:

60662

AN:

249322

AF XY:

0.242

show subpopulations

Gnomad AFR exome

AF:

0.487

Gnomad AMR exome

AF:

0.254

Gnomad ASJ exome

AF:

0.169

Gnomad EAS exome

AF:

0.324

Gnomad FIN exome

AF:

0.210

Gnomad NFE exome

AF:

0.175

Gnomad OTH exome

AF:

0.227

GnomAD4 exome

AF:

0.199

AC:

290834

AN:

1458620

Hom.:

32628

Cov.:

AF XY:

0.203

AC XY:

146981

AN XY:

725010

show subpopulations

African (AFR)

AF:

0.494

AC:

16509

AN:

33426

American (AMR)

AF:

0.249

AC:

11097

AN:

44508

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

4353

AN:

26032

East Asian (EAS)

AF:

0.285

AC:

11299

AN:

39608

South Asian (SAS)

AF:

0.348

AC:

29935

AN:

86004

European-Finnish (FIN)

AF:

0.206

AC:

10989

AN:

53290

Middle Eastern (MID)

AF:

0.280

AC:

1611

AN:

5756

European-Non Finnish (NFE)

AF:

0.173

AC:

192022

AN:

1109734

Other (OTH)

AF:

0.216

AC:

13019

AN:

60262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

13628

27257

40885

54514

68142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7198

14396

21594

28792

35990

<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:

0.276

AC:

41980

AN:

152258

Hom.:

7134

Cov.:

AF XY:

0.279

AC XY:

20771

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.477

AC:

19798

AN:

41540

American (AMR)

AF:

0.242

AC:

3703

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.175

AC:

607

AN:

3470

East Asian (EAS)

AF:

0.337

AC:

1744

AN:

5176

South Asian (SAS)

AF:

0.357

AC:

1723

AN:

4820

European-Finnish (FIN)

AF:

0.210

AC:

2225

AN:

10616

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.170

AC:

11556

AN:

68006

Other (OTH)

AF:

0.241

AC:

509

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1508

3017

4525

6034

7542

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

422

844

1266

1688

2110

<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:

0.199

Hom.:

7677

Bravo

AF:

0.285

Asia WGS

AF:

0.379

AC:

1318

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Aug 19, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Opsismodysplasia

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.53

(source)

DANN

Benign

0.52

PhyloP100

-2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(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

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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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over