Genetic Variant AQP12A:p.Thr83Thr (chr2-240692199-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198998.3(AQP12A):c.249T>C(p.Thr83Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 1,547,262 control chromosomes in the GnomAD database, including 4,133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 1150 hom., cov: 30)

Exomes 𝑓: 0.012 ( 2983 hom. )

Consequence

AQP12A
NM_198998.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.80

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.05).

BP6

Variant 2-240692199-T-C is Benign according to our data. Variant chr2-240692199-T-C is described in ClinVar as [Benign]. Clinvar id is 1262883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP12A	NM_198998.3 link	c.249T>C	p.Thr83Thr	synonymous_variant	Exon 2 of 4	ENST00000337801.9	NP_945349.1	Q8IXF9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP12A	ENST00000337801.9 link	c.249T>C	p.Thr83Thr	synonymous_variant	Exon 2 of 4	1	NM_198998.3	ENSP00000337144.4		Q8IXF9

Frequencies

GnomAD3 genomes

AF:

0.0497

AC:

6657

AN:

133904

Hom.:

1141

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0362

Gnomad ASJ

AF:

0.0230

Gnomad EAS

AF:

0.0187

Gnomad SAS

AF:

0.0446

Gnomad FIN

AF:

0.00611

Gnomad MID

AF:

0.0292

Gnomad NFE

AF:

0.00714

Gnomad OTH

AF:

0.0392

GnomAD3 exomes

AF:

0.0174

AC:

4115

AN:

236462

Hom.:

769

AF XY:

0.0160

AC XY:

2061

AN XY:

129086

show subpopulations

Gnomad AFR exome

AF:

0.117

Gnomad AMR exome

AF:

0.0186

Gnomad ASJ exome

AF:

0.0156

Gnomad EAS exome

AF:

0.0123

Gnomad SAS exome

AF:

0.0313

Gnomad FIN exome

AF:

0.000826

Gnomad NFE exome

AF:

0.00475

Gnomad OTH exome

AF:

0.0159

GnomAD4 exome

AF:

0.0115

AC:

16263

AN:

1413292

Hom.:

2983

Cov.:

AF XY:

0.0117

AC XY:

8241

AN XY:

703162

show subpopulations

Gnomad4 AFR exome

AF:

0.167

Gnomad4 AMR exome

AF:

0.0263

Gnomad4 ASJ exome

AF:

0.0202

Gnomad4 EAS exome

AF:

0.0121

Gnomad4 SAS exome

AF:

0.0323

Gnomad4 FIN exome

AF:

0.00168

Gnomad4 NFE exome

AF:

0.00513

Gnomad4 OTH exome

AF:

0.0188

GnomAD4 genome

AF:

0.0498

AC:

6678

AN:

133970

Hom.:

1150

Cov.:

AF XY:

0.0496

AC XY:

3228

AN XY:

65130

show subpopulations

Gnomad4 AFR

AF:

0.157

Gnomad4 AMR

AF:

0.0362

Gnomad4 ASJ

AF:

0.0230

Gnomad4 EAS

AF:

0.0185

Gnomad4 SAS

AF:

0.0444

Gnomad4 FIN

AF:

0.00611

Gnomad4 NFE

AF:

0.00711

Gnomad4 OTH

AF:

0.0392

Alfa

AF:

0.0258

Hom.:

181

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 21, 2018

GeneDx

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

-1.1

CADD

Benign

0.17

DANN

Benign

0.64

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

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