12-49962019-TGAA-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PM4_SupportingBP6BS2

The NM_001651.4(AQP5):c.7_9delAAG(p.Lys3del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000704 in 1,436,404 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00082 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00069 ( 1 hom. )

Consequence

AQP5
NM_001651.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 2.83

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 Likely_benign. Variant got -4 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001651.4. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 12-49962019-TGAA-T is Benign according to our data. Variant chr12-49962019-TGAA-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1645185.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.

BS2

High AC in GnomAd4 at 125 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP5	NM_001651.4 link	c.7_9delAAG	p.Lys3del	conservative_inframe_deletion	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.7_9delAAG	p.Lys3del	conservative_inframe_deletion	Exon 1 of 4	1	NM_001651.4	ENSP00000293599.5	P55064
AQP5-AS1	ENST00000550214.1 link	n.258+645_258+647delTTC		intron_variant	Intron 1 of 1	2
AQP5-AS1	ENST00000550530.1 link	n.117+645_117+647delTTC		intron_variant	Intron 1 of 2	3
AQP5-AS1	ENST00000552379.1 link	n.256+645_256+647delTTC		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.000823

AC:

125

AN:

151842

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00114

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00156

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.00123

AC:

191

AN:

155036

Hom.:

AF XY:

0.00117

AC XY:

101

AN XY:

86518

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000650

Gnomad ASJ exome

AF:

0.000792

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00150

Gnomad NFE exome

AF:

0.00199

Gnomad OTH exome

AF:

0.00128

GnomAD4 exome

AF:

0.000690

AC:

886

AN:

1284562

Hom.:

AF XY:

0.000696

AC XY:

438

AN XY:

628978

show subpopulations

Gnomad4 AFR exome

AF:

0.0000755

Gnomad4 AMR exome

AF:

0.0000414

Gnomad4 ASJ exome

AF:

0.000810

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000327

Gnomad4 FIN exome

AF:

0.00226

Gnomad4 NFE exome

AF:

0.000711

Gnomad4 OTH exome

AF:

0.000697

GnomAD4 genome

AF:

0.000823

AC:

125

AN:

151842

Hom.:

Cov.:

AF XY:

0.000796

AC XY:

AN XY:

74162

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00114

Gnomad4 NFE

AF:

0.00156

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.00222

Hom.:

Bravo

AF:

0.000533

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

May 29, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

AQP5: PM4:Supporting, BS1 -

Palmoplantar keratoderma, Bothnian type

Uncertain:1

Jun 29, 2020

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

- -

AQP5-related disorder

Benign:1

Mar 09, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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