12-49962386-T-A

Variant names:

• chr12-49962386-T-A
• rs372046995
• NM_001651.4:c.363+6T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001651.4(AQP5):​c.363+6T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,371,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: AQP5 NM_001651.4 splice_region, intron
• Scores: Splicing: ADA: 0.8057
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.29
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).

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.363+6T>A		splice_region intron	N/A	NP_001642.1	P55064
	AQP5-AS1	NR_110589.1		n.258+281A>T		intron	N/A
	AQP5-AS1	NR_110590.1		n.256+281A>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP5	ENST00000293599.7	TSL:1 MANE Select	c.363+6T>A		splice_region intron	N/A	ENSP00000293599.5	P55064
	AQP5	ENST00000857226.1		c.363+6T>A		splice_region intron	N/A	ENSP00000527285.1
	AQP5-AS1	ENST00000550214.2	TSL:2	n.286+281A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD2 exomes AF: 0.00 AC: 0 AN: 21916 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1371510 Hom.: 0 Cov.: 29 AF XY: 0.00000294 AC XY: 2 AN XY: 680790

African (AFR) AF: 0.00 AC: 0 AN: 25784

American (AMR) AF: 0.00 AC: 0 AN: 40376

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22378

East Asian (EAS) AF: 0.00 AC: 0 AN: 33002

South Asian (SAS) AF: 0.00 AC: 0 AN: 80548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3754

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1070822

Other (OTH) AF: 0.00 AC: 0 AN: 54898

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Benign	0.88
PhyloP100		3.3

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.81
dbscSNV1_RF	Benign	0.57
SpliceAI score (max)		0.010		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: rs372046995; hg19: chr12-50356169;