AQP5 p.Ile45Ser

Variant names:

• chr12-49962151-T-G
• rs398123055
• NM_001651.4:c.134T>G
• AQP5 p.Ile45Ser

Your query was ambiguous. Multiple possible variants found:

• chr12-49962151-T-G
• chr12-49962150-ATC-TCT
• chr12-49962150-AT-TC
• chr12-49962150-ATC-TCA
• chr12-49962150-ATC-TCG
• chr12-49962151-TC-GT

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_001651.4(AQP5):​c.134T>G​(p.Ile45Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AQP5 NM_001651.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.19
• Publications: 5 publications found

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

ACMG classification

Our verdict: Likely_pathogenic. The variant received 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.946
• PP5: Variant 12-49962151-T-G is Pathogenic according to our data. Variant chr12-49962151-T-G is described in ClinVar as Pathogenic. ClinVar VariationId is 65480.Status of the report is no_assertion_criteria_provided, 0 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP5	NM_001651.4	MANE Select	c.134T>G	p.Ile45Ser	missense	Exon 1 of 4	NP_001642.1	P55064
	AQP5-AS1	NR_110589.1		n.258+516A>C		intron	N/A
	AQP5-AS1	NR_110590.1		n.256+516A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP5	ENST00000293599.7	TSL:1 MANE Select	c.134T>G	p.Ile45Ser	missense	Exon 1 of 4	ENSP00000293599.5	P55064
	AQP5	ENST00000857226.1		c.134T>G	p.Ile45Ser	missense	Exon 1 of 3	ENSP00000527285.1
	AQP5-AS1	ENST00000550214.2	TSL:2	n.286+516A>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.000536 Hom.: 0

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Palmoplantar keratoderma, Bothnian type (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.87	D
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T
M_CAP	Pathogenic	0.52	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	0.60	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.2
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Pathogenic	0.81
Sift	Benign	0.043	D
Sift4G	Uncertain	0.044	D
PromoterAI		-0.11	Neutral
Varity_R		0.75
gMVP		0.91
Mutation Taster		=14/86	disease causing (ClinVar)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs398123055;

hg19: chr12-50355934;