10-132704328-A-G

Position:

• chr10-132704328-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005539.5(INPP5A):​c.475-3985A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 152,238 control chromosomes in the GnomAD database, including 52,824 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 0.83 (52824 hom., cov: 34)
• Consequence: INPP5A NM_005539.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690

Genes affected

INPP5A (HGNC:6076): (inositol polyphosphate-5-phosphatase A) The protein encoded by this gene is a membrane-associated type I inositol 1,4,5-trisphosphate (InsP3) 5-phosphatase. InsP3 5-phosphatases hydrolyze Ins(1,4,5)P3, which mobilizes intracellular calcium and acts as a second messenger mediating cell responses to various stimulation. [provided by RefSeq, Jul 2008]

INPP5A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INPP5A	NM_005539.5	c.475-3985A>G		intron_variant		ENST00000368594.8	NP_005530.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INPP5A	ENST00000368594.8	c.475-3985A>G		intron_variant		1	NM_005539.5	ENSP00000357583.3

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126549 AN: 152120 Hom.: 52775 Cov.: 34

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.891

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.959

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.789

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.842

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

GnomAD4 genome AF: 0.832 AC: 126658 AN: 152238 Hom.: 52824 Cov.: 34 AF XY: 0.831 AC XY: 61887 AN XY: 74436

Gnomad4 AFR AF: 0.835

Gnomad4 AMR AF: 0.891

Gnomad4 ASJ AF: 0.877

Gnomad4 EAS AF: 0.959

Gnomad4 SAS AF: 0.819

Gnomad4 FIN AF: 0.789

Gnomad4 NFE AF: 0.814

Gnomad4 OTH AF: 0.845

Alfa AF: 0.811 Hom.: 22261

Bravo AF: 0.840

Asia WGS AF: 0.896 AC: 3118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.55

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

LitVar

Other links and lift over

dbSNP: rs2246288; hg19: chr10-134517832;