NM_014214.3:c.29C>T

Variant names:

• chr18-11981698-C-T
• rs769079475
• NM_014214.3:c.29C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_014214.3(IMPA2):​c.29C>T​(p.Ala10Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000845 in 1,230,560 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00050 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00089 (2 hom.)
• Consequence: IMPA2 NM_014214.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.321
• Publications: 1 publications found

Genes affected

IMPA2 (HGNC:6051): (inositol monophosphatase 2) This locus encodes an inositol monophosphatase. The encoded protein catalyzes the dephosphoylration of inositol monophosphate and plays an important role in phosphatidylinositol signaling. This locus may be associated with susceptibility to bipolar disorder. [provided by RefSeq, Jan 2011]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01946637).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014214.3. 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
	IMPA2	NM_014214.3	MANE Select	c.29C>T	p.Ala10Val	missense	Exon 1 of 8	NP_055029.1	O14732-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPA2	ENST00000269159.8	TSL:1 MANE Select	c.29C>T	p.Ala10Val	missense	Exon 1 of 8	ENSP00000269159.3	O14732-1
	IMPA2	ENST00000383376.9	TSL:1	n.29C>T		non_coding_transcript_exon	Exon 1 of 7	ENSP00000372867.4	Q6PIP6
	IMPA2	ENST00000886600.1		c.29C>T	p.Ala10Val	missense	Exon 1 of 6	ENSP00000556659.1

Frequencies

GnomAD3 genomes AF: 0.000500 AC: 76 AN: 152080 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

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: 0.000868

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.00178 AC: 1 AN: 562 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.00205

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000894 AC: 964 AN: 1078372 Hom.: 2 Cov.: 31 AF XY: 0.000938 AC XY: 478 AN XY: 509686

African (AFR) AF: 0.0000439 AC: 1 AN: 22764

American (AMR) AF: 0.000845 AC: 7 AN: 8284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14210

East Asian (EAS) AF: 0.00 AC: 0 AN: 26364

South Asian (SAS) AF: 0.00 AC: 0 AN: 20274

European-Finnish (FIN) AF: 0.0000473 AC: 1 AN: 21148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2914

European-Non Finnish (NFE) AF: 0.00101 AC: 927 AN: 918948

Other (OTH) AF: 0.000644 AC: 28 AN: 43466

GnomAD4 genome AF: 0.000499 AC: 76 AN: 152188 Hom.: 0 Cov.: 33 AF XY: 0.000403 AC XY: 30 AN XY: 74400

African (AFR) AF: 0.000241 AC: 10 AN: 41538

American (AMR) AF: 0.000327 AC: 5 AN: 15306

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000868 AC: 59 AN: 67978

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000476 Hom.: 0

Bravo AF: 0.000563

ExAC AF: 0.000126 AC: 5

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	0.11
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	11
DANN	Benign	0.96
DEOGEN2	Benign	0.24	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.52	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.32
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.028
Sift	Benign	0.51	T
Sift4G	Benign	0.13	T
Polyphen		0.0010	B
Vest4		0.11
MVP		0.12
MPC		0.45
ClinPred		0.047	T
GERP RS		1.6
PromoterAI		-0.065	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.022
gMVP		0.38
Mutation Taster		=86/14	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: rs769079475; hg19: chr18-11981697;