Variant 1-154324461-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_080429.3(AQP10):c.887T>C(p.Met296Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

AQP10
NM_080429.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.30

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026867807).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP10	NM_080429.3 link	c.887T>C	p.Met296Thr	missense_variant	Exon 6 of 6	ENST00000324978.8	NP_536354.2	Q96PS8-1
AQP10	XM_011510104.3 link	c.890T>C	p.Met297Thr	missense_variant	Exon 6 of 6		XP_011508406.1
AQP10	XM_047433547.1 link	c.623T>C	p.Met208Thr	missense_variant	Exon 5 of 5		XP_047289503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP10	ENST00000324978.8 link	c.887T>C	p.Met296Thr	missense_variant	Exon 6 of 6	1	NM_080429.3	ENSP00000318355.3		Q96PS8-1
AQP10	ENST00000484864.1 link	c.*567T>C		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000420341.1		Q96PS8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461300

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726968

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 22, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.887T>C (p.M296T) alteration is located in exon 6 (coding exon 6) of the AQP10 gene. This alteration results from a T to C substitution at nucleotide position 887, causing the methionine (M) at amino acid position 296 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

0.091

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.0030

DANN

Benign

0.84

DEOGEN2

Benign

0.022

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.25

M_CAP

Benign

0.023

MetaRNN

Benign

0.027

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.29

PROVEAN

Benign

0.050

REVEL

Benign

0.21

Sift

Benign

0.64

Sift4G

Benign

0.63

Polyphen

0.0

Vest4

0.041

MutPred

0.14

Gain of phosphorylation at M296 (P = 0.0471);

MVP

0.26

MPC

0.84

ClinPred

0.055

GERP RS

-7.0

Varity_R

0.051

gMVP

0.74

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over