Variant 15-68783027-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong

The NM_006305.4(ANP32A):c.553G>A(p.Val185Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000902 in 1,551,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

ANP32A
NM_006305.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.524

Variant links:

Genes affected

ANP32A (HGNC:13233): (acidic nuclear phosphoprotein 32 family member A) Enables RNA binding activity. Involved in nucleocytoplasmic transport. Located in endoplasmic reticulum; nucleus; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ANP32A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, ANP32A

BP4

Computational evidence support a benign effect (MetaRNN=0.058225036).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANP32A	NM_006305.4 linkuse as main transcript	c.553G>A	p.Val185Ile	missense_variant	5/7	ENST00000465139.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANP32A	ENST00000465139.6 linkuse as main transcript	c.553G>A	p.Val185Ile	missense_variant	5/7	1	NM_006305.4	P2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000857

AC:

AN:

1399550

Hom.:

Cov.:

AF XY:

0.0000101

AC XY:

AN XY:

690296

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000280

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:

0.00000649

Gnomad4 OTH exome

AF:

0.0000344

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000986

Hom.:

Bravo

AF:

0.0000264

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2023

The c.553G>A (p.V185I) alteration is located in exon 5 (coding exon 5) of the ANP32A gene. This alteration results from a G to A substitution at nucleotide position 553, causing the valine (V) at amino acid position 185 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.72

Cadd

Benign

Dann

Benign

0.95

DEOGEN2

Benign

0.16

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.55

M_CAP

Benign

0.017

MetaRNN

Benign

0.058

MetaSVM

Benign

-0.61

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.37

REVEL

Benign

0.14

Sift

Benign

0.99

Sift4G

Benign

0.47

Polyphen

0.018

Vest4

0.10

MutPred

0.27

Loss of sheet (P = 0.1158);

MVP

0.34

MPC

0.90

ClinPred

0.31

GERP RS

1.4

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

3.8

Varity_R

0.038

gMVP

0.0091

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over