Genetic Variant AQP12A:p.Thr44Met (chr2-240692081-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.131C>T(p.Thr44Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 1,436,376 control chromosomes in the GnomAD database, including 4 homozygotes. 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 Likely benign (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.000013 ( 4 hom. )

Consequence

AQP12A
NM_198998.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0120

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=0.018270016).

BP6

Variant 2-240692081-C-T is Benign according to our data. Variant chr2-240692081-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3887223.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 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.131C>T	p.Thr44Met	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.131C>T	p.Thr44Met	missense	Exon 2 of 4	ENSP00000337144.4	Q8IXF9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000209

AC:

AN:

239380

AF XY:

0.0000230

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.0000578

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.0000132

AC:

AN:

1436376

Hom.:

Cov.:

AF XY:

0.0000154

AC XY:

AN XY:

714996

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32034

American (AMR)

AF:

0.00

AC:

AN:

38812

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25904

East Asian (EAS)

AF:

0.0000534

AC:

AN:

37426

South Asian (SAS)

AF:

0.00

AC:

AN:

84036

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52872

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5342

European-Non Finnish (NFE)

AF:

0.0000145

AC:

AN:

1100668

Other (OTH)

AF:

0.0000169

AC:

AN:

59282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

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

Cov.:

Alfa

AF:

0.0000284

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000352

AC:

ExAC

AF:

0.0000338

AC:

EpiCase

AF:

0.0000549

EpiControl

AF:

0.00

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

0.068

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.066

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.042

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0056

LIST_S2

Benign

0.52

M_CAP

Benign

0.0020

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.84

PhyloP100

0.012

PrimateAI

Uncertain

0.62

PROVEAN

Benign

0.43

REVEL

Benign

0.022

Sift

Benign

0.64

Sift4G

Benign

1.0

Polyphen

0.0060

Vest4

0.049

MVP

0.055

MPC

0.36

ClinPred

0.033

GERP RS

-2.5

PromoterAI

-0.018

Neutral

(source)

Varity_R

0.012

gMVP

0.47

Mutation Taster

=98/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over