chr2-240692199-T-C

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

2

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]

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
AQP12ANM_198998.3 linkc.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
AQP12AENST00000337801.9 linkc.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.:
30
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.:
90
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.:
30
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.

Other links and lift over

dbSNP: rs11889147; hg19: chr2-241631616; COSMIC: COSV61836565; COSMIC: COSV61836565; API