rs12780199

Positions:

• chr10-132740405-A-G
• chr10-132740405-A-T

Variant summary

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

The NM_005539.5(INPP5A):​c.733-9112A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,128 control chromosomes in the GnomAD database, including 5,321 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 0.25 (5321 hom., cov: 32)
• Consequence: INPP5A NM_005539.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.32

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INPP5A	NM_005539.5	c.733-9112A>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.733-9112A>G		intron_variant		1	NM_005539.5	ENSP00000357583	P1
INPP5A	ENST00000368593.7	c.733-9112A>G		intron_variant		1		ENSP00000357582
INPP5A	ENST00000342652.6	c.646+13500A>G		intron_variant		5		ENSP00000340707
INPP5A	ENST00000498337.1	n.195-9112A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38407 AN: 152010 Hom.: 5316 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.253 AC: 38430 AN: 152128 Hom.: 5321 Cov.: 32 AF XY: 0.251 AC XY: 18699 AN XY: 74366

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.260

Alfa AF: 0.289 Hom.: 6704

Bravo AF: 0.239

Asia WGS AF: 0.195 AC: 679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.060
DANN	Benign	0.26

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: rs12780199; hg19: chr10-134553909;