Variant 12-49962372-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_001651.4(AQP5):c.355G>A(p.Val119Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000836 in 1,435,050 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000084 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AQP5
NM_001651.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0800

Variant links:

Genes affected

AQP5 (HGNC:638): (aquaporin 5) Aquaporin 5 (AQP5) is a water channel protein. Aquaporins are a family of small integral membrane proteins related to the major intrinsic protein (MIP or AQP0). Aquaporin 5 plays a role in the generation of saliva, tears and pulmonary secretions. AQP0, AQP2, AQP5, and AQP6 are closely related and all map to 12q13. [provided by RefSeq, Jul 2008]

AQP5 links:

AQP5-AS1 (HGNC:55474): (AQP5 and AQP2 antisense RNA 2)

AQP5-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16956523).

BP6

Variant 12-49962372-G-A is Benign according to our data. Variant chr12-49962372-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2608648.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP5	NM_001651.4 link	c.355G>A	p.Val119Ile	missense_variant	Exon 1 of 4	ENST00000293599.7	NP_001642.1	P55064

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AQP5	ENST00000293599.7 link	c.355G>A	p.Val119Ile	missense_variant	Exon 1 of 4	1	NM_001651.4	ENSP00000293599.5	P55064
AQP5-AS1	ENST00000550214.1 link	n.258+295C>T		intron_variant	Intron 1 of 1	2
AQP5-AS1	ENST00000550530.1 link	n.117+295C>T		intron_variant	Intron 1 of 2	3
AQP5-AS1	ENST00000552379.1 link	n.256+295C>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

132730

Hom.:

Cov.:

FAILED QC

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000836

AC:

AN:

1435050

Hom.:

Cov.:

AF XY:

0.00000841

AC XY:

AN XY:

713340

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000789

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000815

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

132830

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

64040

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:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000417

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.35

CADD

Benign

6.2

DANN

Benign

0.94

DEOGEN2

Benign

0.39

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.64

M_CAP

Benign

0.058

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.42

MutationAssessor

Benign

0.52

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.090

REVEL

Benign

0.20

Sift

Benign

0.29

Sift4G

Benign

0.35

Polyphen

0.010

Vest4

0.094

MutPred

0.56

Loss of methylation at R114 (P = 0.1542);

MVP

0.62

MPC

0.30

ClinPred

0.032

GERP RS

2.8

Varity_R

0.049

gMVP

0.40

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