rs562978775

Variant names:

• chr10-119804197-G-T
• rs562978775
• NM_014937.4:c.1141G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014937.4(INPP5F):​c.1141G>T​(p.Ala381Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 1,610,258 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000023 (1 hom.)
• Consequence: INPP5F NM_014937.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.98
• Publications: 0 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]

ENSG00000293336 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.038731307).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014937.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPP5F	NM_014937.4	MANE Select	c.1141G>T	p.Ala381Ser	missense	Exon 10 of 20	NP_055752.1	Q9Y2H2-1
	INPP5F	NM_001441000.1		c.1141G>T	p.Ala381Ser	missense	Exon 10 of 20	NP_001427929.1
	INPP5F	NM_001441001.1		c.1090G>T	p.Ala364Ser	missense	Exon 11 of 21	NP_001427930.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPP5F	ENST00000650623.2	MANE Select	c.1141G>T	p.Ala381Ser	missense	Exon 10 of 20	ENSP00000497527.1	Q9Y2H2-1
	INPP5F	ENST00000964566.1		c.1141G>T	p.Ala381Ser	missense	Exon 10 of 21	ENSP00000634625.1
	INPP5F	ENST00000895117.1		c.1084G>T	p.Ala362Ser	missense	Exon 9 of 19	ENSP00000565176.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000240 AC: 6 AN: 250328 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000226 AC: 33 AN: 1457948 Hom.: 1 Cov.: 28 AF XY: 0.0000345 AC XY: 25 AN XY: 725630

African (AFR) AF: 0.00 AC: 0 AN: 33384

American (AMR) AF: 0.00 AC: 0 AN: 44236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39618

South Asian (SAS) AF: 0.000209 AC: 18 AN: 85972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109284

Other (OTH) AF: 0.000166 AC: 10 AN: 60242

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152310 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74488

African (AFR) AF: 0.00 AC: 0 AN: 41556

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000576 AC: 7

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.58
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.81	N
PhyloP100		3.0
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.92	N
REVEL	Benign	0.049
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.23
MutPred		0.33		Gain of disorder (P = 0.0501)
MVP		0.21
MPC		0.12
ClinPred		0.014	T
GERP RS		1.7
Varity_R		0.025
gMVP		0.27
Mutation Taster		=90/10	polymorphism

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: rs562978775; hg19: chr10-121563709;