17-1500183-G-T

Variant names:

• chr17-1500183-G-T
• rs1109303
• NM_016532.4:c.777-2061C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016532.4(INPP5K):​c.777-2061C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 152,108 control chromosomes in the GnomAD database, including 30,057 homozygotes. 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: 𝑓 0.63 (30057 hom., cov: 33)
• Consequence: INPP5K NM_016532.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.295
• Publications: 17 publications found

Genes affected

INPP5K (HGNC:33882): (inositol polyphosphate-5-phosphatase K) This gene encodes a protein with 5-phosphatase activity toward polyphosphate inositol. The protein localizes to the cytosol in regions lacking actin stress fibers. It is thought that this protein may negatively regulate the actin cytoskeleton. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2008]

INPP5K Gene-Disease associations (from GenCC):

• congenital muscular dystrophy with cataracts and intellectual disability

  Inheritance: AR Classification: STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Marinesco-Sjogren syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016532.4. 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
	INPP5K	NM_016532.4	MANE Select	c.777-2061C>A		intron	N/A	NP_057616.2
	INPP5K	NM_001135642.2		c.549-2061C>A		intron	N/A	NP_001129114.1	Q9BT40-2
	INPP5K	NM_130766.3		c.549-2061C>A		intron	N/A	NP_570122.1	Q9BT40-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPP5K	ENST00000421807.7	TSL:1 MANE Select	c.777-2061C>A		intron	N/A	ENSP00000413937.2	Q9BT40-1
	INPP5K	ENST00000898974.1		c.864-2061C>A		intron	N/A	ENSP00000569033.1
	INPP5K	ENST00000898971.1		c.819-2061C>A		intron	N/A	ENSP00000569030.1

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95127 AN: 151990 Hom.: 30026 Cov.: 33

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.612

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.626 AC: 95203 AN: 152108 Hom.: 30057 Cov.: 33 AF XY: 0.620 AC XY: 46091 AN XY: 74344

African (AFR) AF: 0.686 AC: 28462 AN: 41518

American (AMR) AF: 0.552 AC: 8436 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2285 AN: 3468

East Asian (EAS) AF: 0.383 AC: 1981 AN: 5168

South Asian (SAS) AF: 0.545 AC: 2628 AN: 4822

European-Finnish (FIN) AF: 0.626 AC: 6610 AN: 10560

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42751 AN: 67974

Other (OTH) AF: 0.612 AC: 1293 AN: 2114

Alfa AF: 0.622 Hom.: 126386

Bravo AF: 0.620

Asia WGS AF: 0.512 AC: 1781 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.89
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1109303;

hg19: chr17-1403477;