chr1-154323754-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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]

ENSG00000305636 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39230493).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080429.3. 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
	AQP10	NM_080429.3	MANE Select	c.655C>G	p.Leu219Val	missense	Exon 5 of 6	NP_536354.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP10	ENST00000324978.8	TSL:1 MANE Select	c.655C>G	p.Leu219Val	missense	Exon 5 of 6	ENSP00000318355.3	Q96PS8-1
	AQP10	ENST00000484864.1	TSL:1	c.655C>G	p.Leu219Val	missense	Exon 5 of 5	ENSP00000420341.1	Q96PS8-2
	AQP10	ENST00000908289.1		c.658C>G	p.Leu220Val	missense	Exon 5 of 6	ENSP00000578348.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	0.19
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
M_CAP	Uncertain	0.093	D
MetaRNN	Benign	0.39	T
MetaSVM	Uncertain	-0.041	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		0.15
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.58
Sift	Benign	0.052	T
Sift4G	Uncertain	0.033	D
Polyphen		0.058	B
Vest4		0.21
MutPred		0.74		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
Mutation Taster		=81/19	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

hg19: chr1-154296230;