1-154323754-C-G

Variant names:

• chr1-154323754-C-G
• NM_080429.3:c.655C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_080429.3(AQP10):​c.655C>G​(p.Leu219Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AQP10 NM_080429.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.151

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]

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=0.39230493).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP10	NM_080429.3	c.655C>G	p.Leu219Val	missense_variant	Exon 5 of 6	ENST00000324978.8	NP_536354.2
AQP10	XM_011510104.3	c.658C>G	p.Leu220Val	missense_variant	Exon 5 of 6		XP_011508406.1
AQP10	XM_047433547.1	c.391C>G	p.Leu131Val	missense_variant	Exon 4 of 5		XP_047289503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP10	ENST00000324978.8	c.655C>G	p.Leu219Val	missense_variant	Exon 5 of 6	1	NM_080429.3	ENSP00000318355.3
AQP10	ENST00000484864.1	c.655C>G	p.Leu219Val	missense_variant	Exon 5 of 5	1		ENSP00000420341.1
AQP10	ENST00000355197.4	n.594C>G		non_coding_transcript_exon_variant	Exon 4 of 4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.655C>G (p.L219V) alteration is located in exon 5 (coding exon 5) of the AQP10 gene. This alteration results from a C to G substitution at nucleotide position 655, causing the leucine (L) at amino acid position 219 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	0.19
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.38	T;.
Eigen	Benign	-0.031
Eigen_PC	Benign	-0.059
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.80	T;T
M_CAP	Uncertain	0.093	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Uncertain	-0.041	T
MutationAssessor	Pathogenic	3.1	M;M
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.9	N;N
REVEL	Uncertain	0.58
Sift	Benign	0.052	T;D
Sift4G	Uncertain	0.033	D;D
Polyphen		0.058	B;P
Vest4		0.21
MutPred		0.74		Gain of catalytic residue at L219 (P = 0.0893);Gain of catalytic residue at L219 (P = 0.0893);
MVP		0.82
MPC		1.1
ClinPred		0.67	D
GERP RS		1.8
Varity_R		0.48
gMVP		0.66

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: chr1-154296230;