10-119791605-C-T

Variant names:

• chr10-119791605-C-T
• rs903287908
• NM_014937.4:c.404C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001441015.1(INPP5F):​c.-101C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0000137 in 1,604,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.000013 (0 hom.)
• Consequence: INPP5F NM_001441015.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.60
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33984792).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001441015.1. 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.404C>T	p.Thr135Met	missense	Exon 4 of 20	NP_055752.1	Q9Y2H2-1
	INPP5F	NM_001441015.1		c.-101C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 19	NP_001427944.1
	INPP5F	NM_001441017.1		c.-294C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 20	NP_001427946.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPP5F	ENST00000650623.2	MANE Select	c.404C>T	p.Thr135Met	missense	Exon 4 of 20	ENSP00000497527.1	Q9Y2H2-1
	INPP5F	ENST00000369081.3	TSL:1	c.404C>T	p.Thr135Met	missense	Exon 4 of 5	ENSP00000489864.1	Q9Y2H2-3
	INPP5F	ENST00000964566.1		c.404C>T	p.Thr135Met	missense	Exon 4 of 21	ENSP00000634625.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000131 AC: 19 AN: 1452544 Hom.: 0 Cov.: 28 AF XY: 0.0000111 AC XY: 8 AN XY: 723190

African (AFR) AF: 0.00 AC: 0 AN: 33278

American (AMR) AF: 0.0000447 AC: 2 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39588

South Asian (SAS) AF: 0.00 AC: 0 AN: 86038

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52730

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5722

European-Non Finnish (NFE) AF: 0.0000118 AC: 13 AN: 1104324

Other (OTH) AF: 0.0000499 AC: 3 AN: 60096

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152146 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74328

African (AFR) AF: 0.00 AC: 0 AN: 41420

American (AMR) AF: 0.000196 AC: 3 AN: 15278

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

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

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000604

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	0.14
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.6
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.21
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.36
MutPred		0.45		Gain of sheet (P = 0.0125)
MVP		0.51
MPC		0.53
ClinPred		0.87	D
GERP RS		5.6
Varity_R		0.14
gMVP		0.30
Mutation Taster		=47/53	disease causing

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: rs903287908; hg19: chr10-121551117;