NM_080429.3:c.367C>T

Variant names:

• chr1-154323116-C-T
• rs6685323
• NM_080429.3:c.367C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080429.3(AQP10):​c.367C>T​(p.His123Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,613,838 control chromosomes in the GnomAD database, including 76,311 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.30 (6928 hom., cov: 32)
  • Exomes 𝑓: 0.31 (69383 hom.)
• Consequence: AQP10 NM_080429.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 28 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029536784).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

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.367C>T	p.His123Tyr	missense	Exon 3 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.367C>T	p.His123Tyr	missense	Exon 3 of 6	ENSP00000318355.3	Q96PS8-1
	AQP10	ENST00000484864.1	TSL:1	c.367C>T	p.His123Tyr	missense	Exon 3 of 5	ENSP00000420341.1	Q96PS8-2
	AQP10	ENST00000908289.1		c.370C>T	p.His124Tyr	missense	Exon 3 of 6	ENSP00000578348.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45717 AN: 151882 Hom.: 6919 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.287

GnomAD2 exomes AF: 0.292 AC: 73523 AN: 251454 AF XY: 0.299

Gnomad AFR exome AF: 0.314

Gnomad AMR exome AF: 0.215

Gnomad ASJ exome AF: 0.209

Gnomad EAS exome AF: 0.227

Gnomad FIN exome AF: 0.367

Gnomad NFE exome AF: 0.303

Gnomad OTH exome AF: 0.287

GnomAD4 exome AF: 0.306 AC: 446718 AN: 1461838 Hom.: 69383 Cov.: 48 AF XY: 0.307 AC XY: 223560 AN XY: 727216

African (AFR) AF: 0.316 AC: 10566 AN: 33478

American (AMR) AF: 0.216 AC: 9671 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 5551 AN: 26136

East Asian (EAS) AF: 0.228 AC: 9042 AN: 39700

South Asian (SAS) AF: 0.346 AC: 29853 AN: 86256

European-Finnish (FIN) AF: 0.361 AC: 19296 AN: 53416

Middle Eastern (MID) AF: 0.262 AC: 1512 AN: 5768

European-Non Finnish (NFE) AF: 0.309 AC: 343081 AN: 1111970

Other (OTH) AF: 0.300 AC: 18146 AN: 60390

GnomAD4 genome AF: 0.301 AC: 45761 AN: 152000 Hom.: 6928 Cov.: 32 AF XY: 0.304 AC XY: 22552 AN XY: 74290

African (AFR) AF: 0.311 AC: 12901 AN: 41464

American (AMR) AF: 0.247 AC: 3768 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 708 AN: 3462

East Asian (EAS) AF: 0.223 AC: 1153 AN: 5168

South Asian (SAS) AF: 0.326 AC: 1571 AN: 4822

European-Finnish (FIN) AF: 0.372 AC: 3926 AN: 10540

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.305 AC: 20707 AN: 67946

Other (OTH) AF: 0.292 AC: 616 AN: 2110

Alfa AF: 0.297 Hom.: 20648

Bravo AF: 0.289

TwinsUK AF: 0.288 AC: 1067

ALSPAC AF: 0.299 AC: 1152

ESP6500AA AF: 0.308 AC: 1358

ESP6500EA AF: 0.296 AC: 2542

ExAC AF: 0.297 AC: 36076

Asia WGS AF: 0.272 AC: 944 AN: 3478

EpiCase AF: 0.299

EpiControl AF: 0.299

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	2.6
DANN	Benign	0.48
DEOGEN2	Benign	0.071	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.99	N
PhyloP100		1.0
PrimateAI	Benign	0.42	T
PROVEAN	Benign	3.7	N
REVEL	Benign	0.21
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.066
MPC		0.85
ClinPred		0.0018	T
GERP RS		3.8
Varity_R		0.16
gMVP		0.65
Mutation Taster		=99/1	polymorphism (auto)

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

dbSNP: rs6685323; hg19: chr1-154295592; COSMIC: COSV61476183; COSMIC: COSV61476183;