chr16-25217354-A-G

Position:

• chr16-25217354-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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: 32)
• Consequence: AQP8 NM_001169.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.77

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AQP8	NM_001169.3	c.169A>G	p.Ile57Val	missense_variant	2/6	ENST00000219660.6	NP_001160.2
AQP8	XM_011545822.3	c.172A>G	p.Ile58Val	missense_variant	2/6		XP_011544124.1
AQP8	XM_011545823.3	c.172A>G	p.Ile58Val	missense_variant	2/4		XP_011544125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AQP8	ENST00000219660.6	c.169A>G	p.Ile57Val	missense_variant	2/6	1	NM_001169.3	ENSP00000219660.5
AQP8	ENST00000566125.5	c.151A>G	p.Ile51Val	missense_variant	2/6	1		ENSP00000454457.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2024

The c.169A>G (p.I57V) alteration is located in exon 2 (coding exon 2) of the AQP8 gene. This alteration results from a A to G substitution at nucleotide position 169, causing the isoleucine (I) at amino acid position 57 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-0.32	T
MutationAssessor	Benign	0.53	.;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.33	N;N
REVEL	Uncertain	0.33
Sift	Benign	0.27	T;T
Sift4G	Benign	0.40	T;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
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-25228675;