15-58173186-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_020980.5(AQP9):c.357C>T(p.Thr119=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000383 in 1,614,088 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (2 hom.)
• Consequence: AQP9 NM_020980.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.457

Genes affected

AQP9 (HGNC:643): (aquaporin 9) The aquaporins are a family of water-selective membrane channels. This gene encodes a member of a subset of aquaporins called the aquaglyceroporins. This protein allows passage of a broad range of noncharged solutes and also stimulates urea transport and osmotic water permeability. This protein may also facilitate the uptake of glycerol in hepatic tissue . The encoded protein may also play a role in specialized leukocyte functions such as immunological response and bactericidal activity. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

ALDH1A2 (HGNC:15472): (aldehyde dehydrogenase 1 family member A2) This protein belongs to the aldehyde dehydrogenase family of proteins. The product of this gene is an enzyme that catalyzes the synthesis of retinoic acid (RA) from retinaldehyde. Retinoic acid, the active derivative of vitamin A (retinol), is a hormonal signaling molecule that functions in developing and adult tissues. The studies of a similar mouse gene suggest that this enzyme and the cytochrome CYP26A1, concurrently establish local embryonic retinoic acid levels which facilitate posterior organ development and prevent spina bifida. Four transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, May 2011]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 15-58173186-C-T is Benign according to our data. Variant chr15-58173186-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2645380.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.457 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AQP9	NM_020980.5	c.357C>T	p.Thr119=	synonymous_variant	3/6	ENST00000219919.9
AQP9	NM_001320636.1	c.162C>T	p.Thr54=	synonymous_variant	3/6
AQP9	NM_001320635.2	c.357C>T	p.Thr119=	synonymous_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AQP9	ENST00000219919.9	c.357C>T	p.Thr119=	synonymous_variant	3/6	1	NM_020980.5	P1

Frequencies

GnomAD3 genomes AF: 0.00196 AC: 298 AN: 152110 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00671

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.000541 AC: 136 AN: 251414 Hom.: 1 AF XY: 0.000397 AC XY: 54 AN XY: 135880

Gnomad AFR exome AF: 0.00671

Gnomad AMR exome AF: 0.000405

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000220 AC: 321 AN: 1461860 Hom.: 2 Cov.: 32 AF XY: 0.000188 AC XY: 137 AN XY: 727234

Gnomad4 AFR exome AF: 0.00615

Gnomad4 AMR exome AF: 0.000514

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000405

Gnomad4 OTH exome AF: 0.000695

GnomAD4 genome AF: 0.00196 AC: 298 AN: 152228 Hom.: 0 Cov.: 32 AF XY: 0.00183 AC XY: 136 AN XY: 74442

Gnomad4 AFR AF: 0.00669

Gnomad4 AMR AF: 0.000981

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00139 Hom.: 1

Bravo AF: 0.00239

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

AQP9: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	9.2
Dann	Benign	0.76

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

Other links and lift over

dbSNP: rs148872883; hg19: chr15-58465385; COSMIC: COSV99582864;