1-154323741-C-A

Variant names:

• chr1-154323741-C-A
• NM_080429.3:c.642C>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_080429.3(AQP10):​c.642C>A​(p.Asn214Lys) 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 pathogenic 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: 0.975

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.98

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP10	NM_080429.3	c.642C>A	p.Asn214Lys	missense_variant	Exon 5 of 6	ENST00000324978.8	NP_536354.2
AQP10	XM_011510104.3	c.645C>A	p.Asn215Lys	missense_variant	Exon 5 of 6		XP_011508406.1
AQP10	XM_047433547.1	c.378C>A	p.Asn126Lys	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.642C>A	p.Asn214Lys	missense_variant	Exon 5 of 6	1	NM_080429.3	ENSP00000318355.3
AQP10	ENST00000484864.1	c.642C>A	p.Asn214Lys	missense_variant	Exon 5 of 5	1		ENSP00000420341.1
AQP10	ENST00000355197.4	n.581C>A		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

Feb 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.642C>A (p.N214K) alteration is located in exon 5 (coding exon 5) of the AQP10 gene. This alteration results from a C to A substitution at nucleotide position 642, causing the asparagine (N) at amino acid position 214 to be replaced by a lysine (K). 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	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.83	D;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Pathogenic	4.6	H;H
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-6.0	D;D
REVEL	Uncertain	0.48
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.96
MutPred		0.86		Gain of catalytic residue at N214 (P = 0.0011);Gain of catalytic residue at N214 (P = 0.0011);
MVP		0.76
MPC		1.9
ClinPred		1.0	D
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.97
gMVP		0.99

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: chr1-154296217;