Variant 1-154323611-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_080429.3(AQP10):c.512T>C(p.Ile171Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

AQP10
NM_080429.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.27

Variant links:

Genes affected

AQP10 (HGNC:16029): (aquaporin 10) This gene encodes a member of the aquaglyceroporin family of integral membrane proteins. Members of this family function as water-permeable channels in the epithelia of organs that absorb and excrete water. This protein was shown to function as a water-selective channel, and could also permeate neutral solutes such as glycerol and urea. [provided by RefSeq, Jul 2008]

AQP10 links:

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ACMG classification

Classification made for transcript

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=0.23199722).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP10	NM_080429.3 link	c.512T>C	p.Ile171Thr	missense_variant	Exon 5 of 6	ENST00000324978.8	NP_536354.2	Q96PS8-1
AQP10	XM_011510104.3 link	c.515T>C	p.Ile172Thr	missense_variant	Exon 5 of 6		XP_011508406.1
AQP10	XM_047433547.1 link	c.248T>C	p.Ile83Thr	missense_variant	Exon 4 of 5		XP_047289503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AQP10	ENST00000324978.8 link	c.512T>C	p.Ile171Thr	missense_variant	Exon 5 of 6	1	NM_080429.3	ENSP00000318355.3	Q96PS8-1
AQP10	ENST00000484864.1 link	c.512T>C	p.Ile171Thr	missense_variant	Exon 5 of 5	1		ENSP00000420341.1	Q96PS8-2
AQP10	ENST00000355197.4 link	n.451T>C		non_coding_transcript_exon_variant	Exon 4 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461640

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000386

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.512T>C (p.I171T) alteration is located in exon 5 (coding exon 5) of the AQP10 gene. This alteration results from a T to C substitution at nucleotide position 512, causing the isoleucine (I) at amino acid position 171 to be replaced by a threonine (T). 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

0.28

BayesDel_addAF

Uncertain

0.022

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.45

T;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.083

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.062

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

0.54

N;N

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.2

D;D

REVEL

Benign

0.24

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.41

B;B

Vest4

0.24

MutPred

0.49

Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);

MVP

0.70

MPC

0.96

ClinPred

0.69

GERP RS

3.8

Varity_R

0.70

gMVP

0.73

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over