10-119798561-C-T

Variant names:

• chr10-119798561-C-T
• rs141370318
• NM_014937.4:c.1067C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014937.4(INPP5F):​c.1067C>T​(p.Ala356Val) variant causes a missense change. The variant allele was found at a frequency of 0.000122 in 1,612,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: INPP5F NM_014937.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.75
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1198715).

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.1067C>T	p.Ala356Val	missense	Exon 9 of 20	NP_055752.1	Q9Y2H2-1
	INPP5F	NM_001441000.1		c.1067C>T	p.Ala356Val	missense	Exon 9 of 20	NP_001427929.1
	INPP5F	NM_001441001.1		c.1016C>T	p.Ala339Val	missense	Exon 10 of 21	NP_001427930.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPP5F	ENST00000650623.2	MANE Select	c.1067C>T	p.Ala356Val	missense	Exon 9 of 20	ENSP00000497527.1	Q9Y2H2-1
	INPP5F	ENST00000964566.1		c.1067C>T	p.Ala356Val	missense	Exon 9 of 21	ENSP00000634625.1
	INPP5F	ENST00000895117.1		c.1010C>T	p.Ala337Val	missense	Exon 8 of 19	ENSP00000565176.1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152038 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000359 AC: 9 AN: 250614 AF XY: 0.0000221

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000705

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000129 AC: 188 AN: 1459920 Hom.: 0 Cov.: 29 AF XY: 0.000121 AC XY: 88 AN XY: 726280

African (AFR) AF: 0.00 AC: 0 AN: 33418

American (AMR) AF: 0.00 AC: 0 AN: 44582

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39518

South Asian (SAS) AF: 0.00 AC: 0 AN: 85918

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53334

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

European-Non Finnish (NFE) AF: 0.000167 AC: 185 AN: 1111012

Other (OTH) AF: 0.0000498 AC: 3 AN: 60300

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152156 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74400

African (AFR) AF: 0.0000482 AC: 2 AN: 41510

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

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

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67994

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

Alfa AF: 0.0000774 Hom.: 0

Bravo AF: 0.0000945

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000577 AC: 7

EpiCase AF: 0.000109

EpiControl AF: 0.000119

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	0.099
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Benign	0.38
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.056
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.0	L
PhyloP100		4.7
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.14
Sift	Benign	0.39	T
Sift4G	Benign	0.97	T
Polyphen		0.0	B
Vest4		0.31
MVP		0.38
MPC		0.13
ClinPred		0.18	T
GERP RS		5.0
Varity_R		0.050
gMVP		0.28
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs141370318; hg19: chr10-121558073;