NM_001567.4:c.50A>T

Variant names:

• chr11-72225034-A-T
• rs1948628587
• NM_001567.4:c.50A>T

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.50A>T​(p.Gln17Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,225,706 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: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: INPPL1 NM_001567.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.209
• 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=0.20606437).

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.50A>T	p.Gln17Leu	missense	Exon 1 of 28	NP_001558.3
	INPPL1	NM_001440434.1		c.50A>T	p.Gln17Leu	missense	Exon 1 of 28	NP_001427363.1
	INPPL1	NM_001440435.1		c.50A>T	p.Gln17Leu	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.50A>T	p.Gln17Leu	missense	Exon 1 of 28	ENSP00000298229.2	O15357-1
	INPPL1	ENST00000924957.1		c.50A>T	p.Gln17Leu	missense	Exon 2 of 29	ENSP00000595016.1
	INPPL1	ENST00000946902.1		c.50A>T	p.Gln17Leu	missense	Exon 2 of 29	ENSP00000616961.1

Frequencies

GnomAD3 genomes AF: 0.00000661 AC: 1 AN: 151208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000223 AC: 24 AN: 1074498 Hom.: 0 Cov.: 30 AF XY: 0.0000118 AC XY: 6 AN XY: 508106

African (AFR) AF: 0.00 AC: 0 AN: 22582

American (AMR) AF: 0.00 AC: 0 AN: 8136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13966

East Asian (EAS) AF: 0.00 AC: 0 AN: 26112

South Asian (SAS) AF: 0.00 AC: 0 AN: 19688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21046

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2902

European-Non Finnish (NFE) AF: 0.0000262 AC: 24 AN: 916984

Other (OTH) AF: 0.00 AC: 0 AN: 43082

GnomAD4 genome AF: 0.00000661 AC: 1 AN: 151208 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 73866

African (AFR) AF: 0.00 AC: 0 AN: 41226

American (AMR) AF: 0.00 AC: 0 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5106

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67744

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.084
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	18
DANN	Benign	0.86
DEOGEN2	Uncertain	0.48	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.34	T
M_CAP	Pathogenic	0.74	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	0.67	N
PhyloP100		0.21
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-6.2	D
REVEL	Uncertain	0.34
Sift	Benign	0.27	T
Sift4G	Benign	0.17	T
Polyphen		0.0	B
Vest4		0.23
MutPred		0.33		Loss of solvent accessibility (P = 0.0635)
MVP		0.12
MPC		0.22
ClinPred		0.30	T
GERP RS		-0.22
PromoterAI		-0.099	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.078
gMVP		0.40
Mutation Taster		=89/11	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: rs1948628587; hg19: chr11-71936078;