rs760665197

Variant names:

• chr10-119781719-A-C
• rs760665197
• NM_014937.4:c.263A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-119781719-A-C
• chr10-119781719-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014937.4(INPP5F):​c.263A>C​(p.Lys88Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,132 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K88R) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: INPP5F NM_014937.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.64
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.263A>C	p.Lys88Thr	missense	Exon 3 of 20	NP_055752.1	Q9Y2H2-1
	INPP5F	NM_001441000.1		c.263A>C	p.Lys88Thr	missense	Exon 3 of 20	NP_001427929.1
	INPP5F	NM_001441001.1		c.212A>C	p.Lys71Thr	missense	Exon 4 of 21	NP_001427930.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPP5F	ENST00000650623.2	MANE Select	c.263A>C	p.Lys88Thr	missense	Exon 3 of 20	ENSP00000497527.1	Q9Y2H2-1
	INPP5F	ENST00000369081.3	TSL:1	c.263A>C	p.Lys88Thr	missense	Exon 3 of 5	ENSP00000489864.1	Q9Y2H2-3
	INPP5F	ENST00000964566.1		c.263A>C	p.Lys88Thr	missense	Exon 3 of 21	ENSP00000634625.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152132 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: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152132 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74304

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15266

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.8	L
PhyloP100		8.6
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.28
Sift	Uncertain	0.020	D
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.85
MutPred		0.59		Loss of ubiquitination at K88 (P = 0.0218)
MVP		0.62
MPC		0.57
ClinPred		0.90	D
GERP RS		6.1
Varity_R		0.36
gMVP		0.68
Mutation Taster		=197/103	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: rs760665197; hg19: chr10-121541231;