Genetic Variant NM_001651.4:c.7_9delAAG (chr12-49962019-TGAA-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -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

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -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 VariationId is 1645185.

BS2

High AC in GnomAd4 at 125 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001651.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AQP5	NM_001651.4	MANE Select	c.7_9delAAG	p.Lys3del	conservative_inframe_deletion	Exon 1 of 4	NP_001642.1	P55064
AQP5-AS1	NR_110589.1		n.258+645_258+647delTTC		intron	N/A
AQP5-AS1	NR_110590.1		n.256+645_256+647delTTC		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AQP5	ENST00000293599.7	TSL:1 MANE Select	c.7_9delAAG	p.Lys3del	conservative_inframe_deletion	Exon 1 of 4	ENSP00000293599.5	P55064
AQP5	ENST00000857226.1		c.7_9delAAG	p.Lys3del	conservative_inframe_deletion	Exon 1 of 3	ENSP00000527285.1
AQP5-AS1	ENST00000550214.2	TSL:2	n.286+645_286+647delTTC		intron	N/A

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

GnomAD2 exomes

AF:

0.00123

AC:

191

AN:

155036

AF XY:

0.00117

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 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

African (AFR)

AF:

0.0000755

AC:

AN:

26498

American (AMR)

AF:

0.0000414

AC:

AN:

24172

Ashkenazi Jewish (ASJ)

AF:

0.000810

AC:

AN:

19760

East Asian (EAS)

AF:

0.00

AC:

AN:

31424

South Asian (SAS)

AF:

0.0000327

AC:

AN:

61124

European-Finnish (FIN)

AF:

0.00226

AC:

105

AN:

46378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4752

European-Non Finnish (NFE)

AF:

0.000711

AC:

724

AN:

1018796

Other (OTH)

AF:

0.000697

AC:

AN:

51658

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

130

173

216

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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

AF:

0.000823

AC:

125

AN:

151842

Hom.:

Cov.:

AF XY:

0.000796

AC XY:

AN XY:

74162

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41428

American (AMR)

AF:

0.000197

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00114

AC:

AN:

10520

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00156

AC:

106

AN:

67862

Other (OTH)

AF:

0.000480

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.00222

Hom.:

Bravo

AF:

0.000533

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

AQP5-related disorder (1)

Palmoplantar keratoderma, Bothnian type (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.8

Mutation Taster

=28/172

disease causing

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over