10-119827370-A-G

Variant names:

• chr10-119827370-A-G
• rs3188055
• NM_014937.4:c.2989A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001441000.1(INPP5F):​c.3010A>G​(p.Asn1004Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 1,613,804 control chromosomes in the GnomAD database, including 87,431 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7209 hom., cov: 32)
  • Exomes 𝑓: 0.33 (80222 hom.)
• Consequence: INPP5F NM_001441000.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.14
• Publications: 46 publications found

Genes affected

INPP5F (HGNC:17054): (inositol polyphosphate-5-phosphatase F) The protein encoded by this gene is an inositol 1,4,5-trisphosphate (InsP3) 5-phosphatase and contains a Sac domain. The activity of this protein is specific for phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004123211).
• BP6: Variant 10-119827370-A-G is Benign according to our data. Variant chr10-119827370-A-G is described in ClinVar as Benign. ClinVar VariationId is 1232724.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001441000.1. 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
	INPP5F	NM_014937.4	MANE Select	c.2989A>G	p.Asn997Asp	missense	Exon 20 of 20	NP_055752.1
	INPP5F	NM_001441000.1		c.3010A>G	p.Asn1004Asp	missense	Exon 20 of 20	NP_001427929.1
	INPP5F	NM_001441001.1		c.2938A>G	p.Asn980Asp	missense	Exon 21 of 21	NP_001427930.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPP5F	ENST00000650623.2	MANE Select	c.2989A>G	p.Asn997Asp	missense	Exon 20 of 20	ENSP00000497527.1
	INPP5F	ENST00000964566.1		c.3010A>G	p.Asn1004Asp	missense	Exon 21 of 21	ENSP00000634625.1
	INPP5F	ENST00000895117.1		c.2932A>G	p.Asn978Asp	missense	Exon 19 of 19	ENSP00000565176.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46243 AN: 151984 Hom.: 7203 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.311

GnomAD2 exomes AF: 0.294 AC: 73838 AN: 251324 AF XY: 0.295

Gnomad AFR exome AF: 0.264

Gnomad AMR exome AF: 0.244

Gnomad ASJ exome AF: 0.273

Gnomad EAS exome AF: 0.188

Gnomad FIN exome AF: 0.348

Gnomad NFE exome AF: 0.329

Gnomad OTH exome AF: 0.312

GnomAD4 exome AF: 0.328 AC: 479499 AN: 1461702 Hom.: 80222 Cov.: 41 AF XY: 0.325 AC XY: 236605 AN XY: 727178

African (AFR) AF: 0.262 AC: 8782 AN: 33474

American (AMR) AF: 0.248 AC: 11083 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 7338 AN: 26130

East Asian (EAS) AF: 0.188 AC: 7444 AN: 39698

South Asian (SAS) AF: 0.263 AC: 22682 AN: 86258

European-Finnish (FIN) AF: 0.348 AC: 18582 AN: 53412

Middle Eastern (MID) AF: 0.309 AC: 1781 AN: 5768

European-Non Finnish (NFE) AF: 0.344 AC: 382603 AN: 1111846

Other (OTH) AF: 0.318 AC: 19204 AN: 60396

GnomAD4 genome AF: 0.304 AC: 46259 AN: 152102 Hom.: 7209 Cov.: 32 AF XY: 0.302 AC XY: 22455 AN XY: 74378

African (AFR) AF: 0.261 AC: 10849 AN: 41502

American (AMR) AF: 0.283 AC: 4330 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 988 AN: 3468

East Asian (EAS) AF: 0.195 AC: 1009 AN: 5180

South Asian (SAS) AF: 0.271 AC: 1308 AN: 4818

European-Finnish (FIN) AF: 0.345 AC: 3654 AN: 10588

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.338 AC: 22962 AN: 67958

Other (OTH) AF: 0.309 AC: 653 AN: 2114

Alfa AF: 0.320 Hom.: 26530

Bravo AF: 0.300

TwinsUK AF: 0.339 AC: 1257

ALSPAC AF: 0.348 AC: 1341

ESP6500AA AF: 0.264 AC: 1164

ESP6500EA AF: 0.331 AC: 2849

ExAC AF: 0.293 AC: 35523

Asia WGS AF: 0.252 AC: 873 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.6
DANN	Benign	0.67
DEOGEN2	Benign	0.081	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.22	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.1
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.11
Sift	Benign	0.21	T
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.031
MPC		0.14
ClinPred		0.0038	T
GERP RS		1.9
Varity_R		0.063
gMVP		0.053
Mutation Taster		=97/3	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: rs3188055; hg19: chr10-121586882; COSMIC: COSV62820297; COSMIC: COSV62820297;