rs111572783

Variant names:

• chr16-25217367-C-T
• rs111572783
• NM_001169.3:c.182C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-25217367-C-T
• chr16-25217367-C-A
• chr16-25217367-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001169.3(AQP8):​c.182C>T​(p.Thr61Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000632 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000055 (0 hom.)
• Consequence: AQP8 NM_001169.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.12
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07894528).

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.182C>T	p.Thr61Met	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.182C>T	p.Thr61Met	missense	Exon 2 of 6	ENSP00000219660.5	O94778
	AQP8	ENST00000566125.5	TSL:1	c.164C>T	p.Thr55Met	missense	Exon 2 of 6	ENSP00000454457.1	A0A0C4DGL6
	AQP8	ENST00000941548.1		c.182C>T	p.Thr61Met	missense	Exon 2 of 5	ENSP00000611607.1

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152098 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000721

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000103 AC: 26 AN: 251218 AF XY: 0.000125

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000617

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000554 AC: 81 AN: 1461832 Hom.: 0 Cov.: 31 AF XY: 0.0000495 AC XY: 36 AN XY: 727210

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.000335 AC: 15 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000432 AC: 48 AN: 1111966

Other (OTH) AF: 0.0000662 AC: 4 AN: 60388

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74428

African (AFR) AF: 0.000120 AC: 5 AN: 41530

American (AMR) AF: 0.000720 AC: 11 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68020

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.0000414 Hom.: 0

Bravo AF: 0.0000869

ExAC AF: 0.000115 AC: 14

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

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	0.12
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	6.3
DANN	Benign	0.97
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.71	N
PhyloP100		-1.1
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.26
Sift	Benign	0.10	T
Sift4G	Benign	0.11	T
Polyphen		0.82	P
Vest4		0.18
MutPred		0.33		Loss of catalytic residue at T61 (P = 0.0535)
MVP		0.79
MPC		0.24
ClinPred		0.035	T
GERP RS		-3.2
PromoterAI		-0.00060	Neutral
Varity_R		0.012
gMVP		0.43
Mutation Taster		=96/4	polymorphism

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: rs111572783; hg19: chr16-25228688; COSMIC: COSV54844698;