chr11-72225010-G-A

Variant names:

• chr11-72225010-G-A
• rs1239738293
• NM_001567.4:c.26G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001567.4(INPPL1):​c.26G>A​(p.Gly9Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000944 in 1,058,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.4e-7 (0 hom.)
• Consequence: INPPL1 NM_001567.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.225
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23053524).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPPL1	NM_001567.4	MANE Select	c.26G>A	p.Gly9Asp	missense	Exon 1 of 28	NP_001558.3
	INPPL1	NM_001440434.1		c.26G>A	p.Gly9Asp	missense	Exon 1 of 28	NP_001427363.1
	INPPL1	NM_001440435.1		c.26G>A	p.Gly9Asp	missense	Exon 2 of 29	NP_001427364.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPPL1	ENST00000298229.7	TSL:1 MANE Select	c.26G>A	p.Gly9Asp	missense	Exon 1 of 28	ENSP00000298229.2	O15357-1
	INPPL1	ENST00000924957.1		c.26G>A	p.Gly9Asp	missense	Exon 2 of 29	ENSP00000595016.1
	INPPL1	ENST00000946902.1		c.26G>A	p.Gly9Asp	missense	Exon 2 of 29	ENSP00000616961.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.44e-7 AC: 1 AN: 1058904 Hom.: 0 Cov.: 30 AF XY: 0.00000200 AC XY: 1 AN XY: 500126

African (AFR) AF: 0.00 AC: 0 AN: 22046

American (AMR) AF: 0.000132 AC: 1 AN: 7584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13220

East Asian (EAS) AF: 0.00 AC: 0 AN: 24648

South Asian (SAS) AF: 0.00 AC: 0 AN: 19442

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2800

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 906762

Other (OTH) AF: 0.00 AC: 0 AN: 41836

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.37	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.43	T
M_CAP	Pathogenic	0.99	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.32	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.23
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.28
Sift	Benign	0.039	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0080	B
Vest4		0.21
MutPred		0.33		Loss of glycosylation at P10 (P = 0.0881)
MVP		0.33
MPC		0.29
ClinPred		0.15	T
GERP RS		1.5
PromoterAI		-0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.045
gMVP		0.59
Mutation Taster		=289/11	polymorphism

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

Other links and lift over

dbSNP: rs1239738293; hg19: chr11-71936054;