rs12780199

Variant names:

• chr10-132740405-A-G
• rs12780199
• NM_005539.5:c.733-9112A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
INPP5A	NM_005539.5	c.733-9112A>G		intron_variant	Intron 9 of 15	ENST00000368594.8	NP_005530.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INPP5A	ENST00000368594.8	c.733-9112A>G		intron_variant	Intron 9 of 15	1	NM_005539.5	ENSP00000357583.3
INPP5A	ENST00000368593.7	c.733-9112A>G		intron_variant	Intron 9 of 12	1		ENSP00000357582.3
INPP5A	ENST00000342652.6	c.645+13500A>G		intron_variant	Intron 8 of 9	5		ENSP00000340707.6
INPP5A	ENST00000498337.1	n.195-9112A>G		intron_variant	Intron 2 of 4	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

African (AFR) AF: 0.156 AC: 6480 AN: 41492

American (AMR) AF: 0.210 AC: 3207 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1365 AN: 3472

East Asian (EAS) AF: 0.129 AC: 666 AN: 5174

South Asian (SAS) AF: 0.222 AC: 1073 AN: 4824

European-Finnish (FIN) AF: 0.330 AC: 3494 AN: 10578

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21398 AN: 67974

Other (OTH) AF: 0.260 AC: 549 AN: 2110

Alfa AF: 0.284 Hom.: 8451

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
PhyloP100		-2.3
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

Other links and lift over

dbSNP: rs12780199; hg19: chr10-134553909;