16-25217354-A-G

Variant names:

• chr16-25217354-A-G
• NM_001169.3:c.169A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001169.3(AQP8):​c.169A>G​(p.Ile57Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AQP8 NM_001169.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.77
• Publications: 0 publications found

Genes affected

AQP8 (HGNC:642): (aquaporin 8) Aquaporin 8 (AQP8) is a water channel protein. Aquaporins are a family of small integral membrane proteins related to the major intrinsic protein (MIP or AQP0). Aquaporin 8 mRNA is found in pancreas and colon but not other tissues. [provided by RefSeq, Jul 2008]

ENSG00000309232 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35999113).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001169.3. 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
	AQP8	NM_001169.3	MANE Select	c.169A>G	p.Ile57Val	missense	Exon 2 of 6	NP_001160.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP8	ENST00000219660.6	TSL:1 MANE Select	c.169A>G	p.Ile57Val	missense	Exon 2 of 6	ENSP00000219660.5	O94778
	AQP8	ENST00000566125.5	TSL:1	c.151A>G	p.Ile51Val	missense	Exon 2 of 6	ENSP00000454457.1	A0A0C4DGL6
	AQP8	ENST00000941548.1		c.169A>G	p.Ile57Val	missense	Exon 2 of 5	ENSP00000611607.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	16
DANN	Benign	0.88
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.0038
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.32	T
MutationAssessor	Benign	0.53	N
PhyloP100		4.8
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.33	N
REVEL	Uncertain	0.33
Sift	Benign	0.27	T
Sift4G	Benign	0.40	T
Polyphen		0.18	B
Vest4		0.33
MutPred		0.56		Loss of helix (P = 0.1299)
MVP		0.80
MPC		0.22
ClinPred		0.64	D
GERP RS		5.5
PromoterAI		-0.024	Neutral
Varity_R		0.051
gMVP		0.32

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

hg19: chr16-25228675;