12-49962050-C-T

Variant names:

• chr12-49962050-C-T
• rs1373414214
• NM_001651.4:c.33C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001651.4(AQP5):​c.33C>T​(p.Leu11Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L11L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AQP5 NM_001651.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13
• Publications: 2 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_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=2.13 with no splicing effect.

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.33C>T	p.Leu11Leu	synonymous	Exon 1 of 4	NP_001642.1	P55064
	AQP5-AS1	NR_110589.1		n.258+617G>A		intron	N/A
	AQP5-AS1	NR_110590.1		n.256+617G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP5	ENST00000293599.7	TSL:1 MANE Select	c.33C>T	p.Leu11Leu	synonymous	Exon 1 of 4	ENSP00000293599.5	P55064
	AQP5	ENST00000857226.1		c.33C>T	p.Leu11Leu	synonymous	Exon 1 of 3	ENSP00000527285.1
	AQP5-AS1	ENST00000550214.2	TSL:2	n.286+617G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	7.5
DANN	Benign	0.97
PhyloP100		2.1
PromoterAI		0.00060	Neutral

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

Other links and lift over

dbSNP: rs1373414214; hg19: chr12-50355833; COSMIC: COSV52230530; COSMIC: COSV52230530;