chr17-1500183-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016532.4(INPP5K):​c.777-2061C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• Marinesco-Sjogren syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPP5K	NM_016532.4	MANE Select	c.777-2061C>G		intron	N/A	NP_057616.2
	INPP5K	NM_001135642.2		c.549-2061C>G		intron	N/A	NP_001129114.1
	INPP5K	NM_130766.3		c.549-2061C>G		intron	N/A	NP_570122.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPP5K	ENST00000421807.7	TSL:1 MANE Select	c.777-2061C>G		intron	N/A	ENSP00000413937.2
	INPP5K	ENST00000320345.10	TSL:5	c.549-2061C>G		intron	N/A	ENSP00000318476.6
	INPP5K	ENST00000406424.8	TSL:5	c.549-2061C>G		intron	N/A	ENSP00000385177.4

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.86
PhyloP100		0.29

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: rs1109303; hg19: chr17-1403477;