chr16-25217248-C-A

Variant names:

• chr16-25217248-C-A
• rs142212512
• NM_001169.3:c.63C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001169.3(AQP8):​c.63C>A​(p.Ser21Arg) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S21S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AQP8 NM_001169.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.623

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09591001).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP8	NM_001169.3	c.63C>A	p.Ser21Arg	missense_variant	Exon 2 of 6	ENST00000219660.6	NP_001160.2
AQP8	XM_011545822.3	c.66C>A	p.Ser22Arg	missense_variant	Exon 2 of 6		XP_011544124.1
AQP8	XM_011545823.3	c.66C>A	p.Ser22Arg	missense_variant	Exon 2 of 4		XP_011544125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP8	ENST00000219660.6	c.63C>A	p.Ser21Arg	missense_variant	Exon 2 of 6	1	NM_001169.3	ENSP00000219660.5
AQP8	ENST00000566125.5	c.45C>A	p.Ser15Arg	missense_variant	Exon 2 of 6	1		ENSP00000454457.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.63
DANN	Benign	0.58
DEOGEN2	Benign	0.11	.;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.46	T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.096	T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.6	.;L
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.92	N;N
REVEL	Benign	0.29
Sift	Benign	0.18	T;T
Sift4G	Benign	0.26	T;T
Polyphen		0.0010	.;B
Vest4		0.19
MutPred		0.31		.;Gain of MoRF binding (P = 0.0206);
MVP		0.53
MPC		0.25
ClinPred		0.096	T
GERP RS		0.78
Varity_R		0.044
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs142212512; hg19: chr16-25228569;