rs1867380

Variant names:

• chr15-58184082-A-C
• rs1867380
• NM_020980.5:c.835A>C

Your query was ambiguous. Multiple possible variants found:

• chr15-58184082-A-C
• chr15-58184082-A-G
• chr15-58184082-A-T

Variant summary

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

The NM_020980.5(AQP9):​c.835A>C​(p.Thr279Pro) variant causes a missense 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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: AQP9 NM_020980.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540
• Publications: 34 publications found

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]

ALDH1A2 Gene-Disease associations (from GenCC):

• diaphragmatic hernia 4, with cardiovascular defects

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

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 (MetaRNN=0.06939337).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP9	NM_020980.5	c.835A>C	p.Thr279Pro	missense_variant	Exon 6 of 6	ENST00000219919.9	NP_066190.2
AQP9	NM_001320636.1	c.640A>C	p.Thr214Pro	missense_variant	Exon 6 of 6		NP_001307565.1
AQP9	NM_001320635.2	c.*35A>C		3_prime_UTR_variant	Exon 5 of 5		NP_001307564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP9	ENST00000219919.9	c.835A>C	p.Thr279Pro	missense_variant	Exon 6 of 6	1	NM_020980.5	ENSP00000219919.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 53

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	3.4
DANN	Benign	0.66
DEOGEN2	Benign	0.022	T;T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.15	T;.;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.069	T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.34	.;N;N
PhyloP100		0.054
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.080	N;N;N
REVEL	Benign	0.17
Sift	Benign	0.24	T;T;T
Sift4G	Benign	0.26	T;T;T
Polyphen		0.0	.;B;B
Vest4		0.071
MutPred		0.23		.;Loss of phosphorylation at T279 (P = 0.0279);Loss of phosphorylation at T279 (P = 0.0279);
MVP		0.67
MPC		0.011
ClinPred		0.049	T
GERP RS		-3.7
Varity_R		0.059
gMVP		0.69

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: rs1867380; hg19: chr15-58476281;