10-132749597-G-A

Variant names:

• chr10-132749597-G-A
• rs143990293
• NM_005539.5:c.813G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_005539.5(INPP5A):​c.813G>A​(p.Ser271Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 1,612,986 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0022 (8 hom.)
• Consequence: INPP5A NM_005539.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.45
• Publications: 2 publications found

Genes affected

INPP5A (HGNC:6076): (inositol polyphosphate-5-phosphatase A) The protein encoded by this gene is a membrane-associated type I inositol 1,4,5-trisphosphate (InsP3) 5-phosphatase. InsP3 5-phosphatases hydrolyze Ins(1,4,5)P3, which mobilizes intracellular calcium and acts as a second messenger mediating cell responses to various stimulation. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 10-132749597-G-A is Benign according to our data. Variant chr10-132749597-G-A is described in ClinVar as [Benign]. Clinvar id is 782211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.45 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INPP5A	NM_005539.5	c.813G>A	p.Ser271Ser	synonymous_variant	Exon 10 of 16	ENST00000368594.8	NP_005530.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INPP5A	ENST00000368594.8	c.813G>A	p.Ser271Ser	synonymous_variant	Exon 10 of 16	1	NM_005539.5	ENSP00000357583.3
INPP5A	ENST00000368593.7	c.813G>A	p.Ser271Ser	synonymous_variant	Exon 10 of 13	1		ENSP00000357582.3
INPP5A	ENST00000498337.1	n.275G>A		non_coding_transcript_exon_variant	Exon 3 of 5	3
INPP5A	ENST00000342652.6	c.646-16176G>A		intron_variant	Intron 8 of 9	5		ENSP00000340707.6

Frequencies

GnomAD3 genomes AF: 0.00181 AC: 276 AN: 152242 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000458

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00300

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00196 AC: 491 AN: 250574 AF XY: 0.00222

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.00145

Gnomad ASJ exome AF: 0.000299

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00293

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00216 AC: 3152 AN: 1460626 Hom.: 8 Cov.: 31 AF XY: 0.00227 AC XY: 1649 AN XY: 726602

African (AFR) AF: 0.000329 AC: 11 AN: 33478

American (AMR) AF: 0.00136 AC: 61 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00265 AC: 229 AN: 86258

European-Finnish (FIN) AF: 0.000421 AC: 22 AN: 52244

Middle Eastern (MID) AF: 0.00971 AC: 56 AN: 5768

European-Non Finnish (NFE) AF: 0.00235 AC: 2617 AN: 1111952

Other (OTH) AF: 0.00255 AC: 154 AN: 60374

GnomAD4 genome AF: 0.00181 AC: 276 AN: 152360 Hom.: 0 Cov.: 34 AF XY: 0.00180 AC XY: 134 AN XY: 74506

African (AFR) AF: 0.000457 AC: 19 AN: 41592

American (AMR) AF: 0.00189 AC: 29 AN: 15304

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4828

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00300 AC: 204 AN: 68036

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00236 Hom.: 0

Bravo AF: 0.00184

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.80
DANN	Benign	0.83
PhyloP100		-1.4
Mutation Taster		=99/1	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: rs143990293; hg19: chr10-134563101;