1-37945756-G-T

Variant names:

• chr1-37945756-G-T
• NM_005540.3:c.152C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001365825.1(INPP5B):​c.-108C>A variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000000685 in 1,460,328 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: INPP5B NM_001365825.1 5_prime_UTR_premature_start_codon_gain
• Scores: Splicing: ADA: 0.9488
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.92

Genes affected

INPP5B (HGNC:6077): (inositol polyphosphate-5-phosphatase B) This gene encodes a member of a family of inositol polyphosphate-5-phosphatases. These enzymes function in the regulation of calcium signaling by inactivating inositol phosphates. The encoded protein is localized to the cytosol and mitochondria, and associates with membranes through an isoprenyl modification near the C-terminus. Alternatively spliced transcript variants of this gene have been described. [provided by RefSeq, Jul 2014]

LOC105378651 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INPP5B	NM_005540.3	c.152C>A	p.Ala51Asp	missense_variant, splice_region_variant	Exon 3 of 24	ENST00000373024.8	NP_005531.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INPP5B	ENST00000373024.8	c.152C>A	p.Ala51Asp	missense_variant, splice_region_variant	Exon 3 of 24	1	NM_005540.3	ENSP00000362115.3
INPP5B	ENST00000373026.5	c.152C>A	p.Ala51Asp	missense_variant, splice_region_variant	Exon 2 of 23	5		ENSP00000362117.1
INPP5B	ENST00000373021.1	c.152C>A	p.Ala51Asp	missense_variant, splice_region_variant	Exon 2 of 6	1		ENSP00000362112.1
INPP5B	ENST00000491406.2	n.240C>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 3 of 7	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460328 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726538

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T;T;T;.;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.78	T;.;T;T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.59	D;D;D;D;D
MetaSVM	Pathogenic	0.81	D
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.6	.;N;N;N;D
REVEL	Uncertain	0.61
Sift	Pathogenic	0.0	.;D;D;D;D
Sift4G	Benign	0.073	T;D;D;T;D
Polyphen		1.0	.;.;.;D;.
Vest4		0.82
MutPred		0.41		Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);
MVP		0.97
MPC		0.97
ClinPred		1.0	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.65
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.95
dbscSNV1_RF	Pathogenic	0.83
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-38411428;