Genetic Variant AQP12A:p.Ala70Val (chr2-240692159-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_198998.3(AQP12A):c.209C>T(p.Ala70Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 1,583,544 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000069 ( 2 hom., cov: 30)

Exomes 𝑓: 0.0000083 ( 3 hom. )

Consequence

AQP12A
NM_198998.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.189

Publications

0 publications found

Variant links:

Genes affected

AQP12A (HGNC:19941): (aquaporin 12A) Predicted to enable channel activity. Predicted to be involved in transmembrane transport. Predicted to be integral component of membrane. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

AQP12A links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06236118).

BP6

Variant 2-240692159-C-T is Benign according to our data. Variant chr2-240692159-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2595328.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198998.3. 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
	AQP12A	NM_198998.3	MANE Select	c.209C>T	p.Ala70Val	missense	Exon 2 of 4	NP_945349.1	Q8IXF9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP12A	ENST00000337801.9	TSL:1 MANE Select	c.209C>T	p.Ala70Val	missense	Exon 2 of 4	ENSP00000337144.4	Q8IXF9

Frequencies

GnomAD3 genomes

AF:

0.0000688

AC:

AN:

145326

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000220

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:

0.000104

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000249

AC:

AN:

241230

AF XY:

0.0000152

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000574

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000834

AC:

AN:

1438218

Hom.:

Cov.:

AF XY:

0.00000838

AC XY:

AN XY:

715804

show subpopulations

African (AFR)

AF:

0.0000307

AC:

AN:

32612

American (AMR)

AF:

0.00

AC:

AN:

39064

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25978

East Asian (EAS)

AF:

0.0000266

AC:

AN:

37530

South Asian (SAS)

AF:

0.0000713

AC:

AN:

84096

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52838

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5366

European-Non Finnish (NFE)

AF:

0.00000363

AC:

AN:

1101270

Other (OTH)

AF:

0.00

AC:

AN:

59464

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000688

AC:

AN:

145326

Hom.:

Cov.:

AF XY:

0.0000706

AC XY:

AN XY:

70808

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38102

American (AMR)

AF:

0.000220

AC:

AN:

13662

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3406

East Asian (EAS)

AF:

0.00

AC:

AN:

4742

South Asian (SAS)

AF:

0.00

AC:

AN:

4606

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10464

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.000104

AC:

AN:

67146

Other (OTH)

AF:

0.00

AC:

AN:

1990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000253

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.36

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.14

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.54

M_CAP

Benign

0.0023

MetaRNN

Benign

0.062

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.7

PhyloP100

-0.19

PrimateAI

Benign

0.47

PROVEAN

Benign

1.7

REVEL

Benign

0.027

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0050

Vest4

0.028

MutPred

0.55

Gain of helix (P = 0.1736)

MVP

0.061

MPC

0.34

ClinPred

0.016

GERP RS

-3.6

PromoterAI

-0.0034

Neutral

(source)

Varity_R

0.021

gMVP

0.24

Mutation Taster

=97/3

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over