9-33385243-C-A

Variant names:

• chr9-33385243-C-A
• rs62542743
• NM_001170.3:c.791G>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 1P and 12B. PP3 BP4_Strong BA1

The NM_001170.3(AQP7):​c.791G>T​(p.Gly264Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0464 in 1,611,704 control chromosomes in the GnomAD database, including 1,902 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Affects (no stars).

• Frequency:
  • Genomes: 𝑓 0.034 (121 hom., cov: 32)
  • Exomes 𝑓: 0.048 (1781 hom.)
• Consequence: AQP7 NM_001170.3 missense
• Clinical Significance: Affects no assertion criteria provided O:1
• Conservation: PhyloP100: 7.81

Genes affected

AQP7 (HGNC:640): (aquaporin 7) This gene encodes a member of the aquaporin family of water-selective membrane channels. The encoded protein localizes to the plasma membrane and allows movement of water, glycerol and urea across cell membranes. This gene is highly expressed in the adipose tissue where the encoded protein facilitates efflux of glycerol. In the proximal straight tubules of kidney, the encoded protein is localized to the apical membrane and prevents excretion of glycerol into urine. The encoded protein is present in spermatids, as well as in the testicular and epididymal spermatozoa suggesting an important role in late spermatogenesis. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. This gene is located adjacent to a related aquaporin gene on chromosome 9. Multiple pseudogenes of this gene have been identified. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• PP3: Multiple lines of computational evidence support a deleterious effect 6: AlphaMissense, BayesDel_noAF, Cadd, Eigen, phyloP100way_vertebrate, PROVEAN [when BayesDel_addAF, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]
• BP4: Computational evidence support a benign effect (MetaRNN=0.008925259).
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP7	NM_001170.3	c.791G>T	p.Gly264Val	missense_variant	Exon 8 of 8	ENST00000297988.6	NP_001161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP7	ENST00000297988.6	c.791G>T	p.Gly264Val	missense_variant	Exon 8 of 8	1	NM_001170.3	ENSP00000297988.1

Frequencies

GnomAD3 genomes AF: 0.0343 AC: 5216 AN: 152116 Hom.: 121 Cov.: 32

Gnomad AFR AF: 0.00895

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0366

Gnomad ASJ AF: 0.0438

Gnomad EAS AF: 0.0270

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.0494

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0476

Gnomad OTH AF: 0.0359

GnomAD2 exomes AF: 0.0380 AC: 9510 AN: 250394 AF XY: 0.0384

Gnomad AFR exome AF: 0.00763

Gnomad AMR exome AF: 0.0249

Gnomad ASJ exome AF: 0.0402

Gnomad EAS exome AF: 0.0311

Gnomad FIN exome AF: 0.0457

Gnomad NFE exome AF: 0.0489

Gnomad OTH exome AF: 0.0444

GnomAD4 exome AF: 0.0476 AC: 69509 AN: 1459470 Hom.: 1781 Cov.: 32 AF XY: 0.0471 AC XY: 34227 AN XY: 726050

Gnomad4 AFR exome AF: 0.00677 AC: 226 AN: 33406

Gnomad4 AMR exome AF: 0.0267 AC: 1193 AN: 44710

Gnomad4 ASJ exome AF: 0.0419 AC: 1094 AN: 26126

Gnomad4 EAS exome AF: 0.0223 AC: 886 AN: 39696

Gnomad4 SAS exome AF: 0.0266 AC: 2288 AN: 86158

Gnomad4 FIN exome AF: 0.0472 AC: 2516 AN: 53276

Gnomad4 NFE exome AF: 0.0527 AC: 58633 AN: 1111758

Gnomad4 Remaining exome AF: 0.0425 AC: 2561 AN: 60204

GnomAD4 genome AF: 0.0343 AC: 5217 AN: 152234 Hom.: 121 Cov.: 32 AF XY: 0.0347 AC XY: 2583 AN XY: 74424

Gnomad4 AFR AF: 0.00893 AC: 0.00892771 AN: 0.00892771

Gnomad4 AMR AF: 0.0366 AC: 0.0365965 AN: 0.0365965

Gnomad4 ASJ AF: 0.0438 AC: 0.0438293 AN: 0.0438293

Gnomad4 EAS AF: 0.0267 AC: 0.0266925 AN: 0.0266925

Gnomad4 SAS AF: 0.0265 AC: 0.026545 AN: 0.026545

Gnomad4 FIN AF: 0.0494 AC: 0.0493967 AN: 0.0493967

Gnomad4 NFE AF: 0.0476 AC: 0.047638 AN: 0.047638

Gnomad4 OTH AF: 0.0355 AC: 0.035545 AN: 0.035545

Alfa AF: 0.0383 Hom.: 40

Bravo AF: 0.0336

TwinsUK AF: 0.0531 AC: 197

ALSPAC AF: 0.0488 AC: 188

ESP6500AA AF: 0.0116 AC: 51

ESP6500EA AF: 0.0488 AC: 420

ExAC AF: 0.0365 AC: 4433

Asia WGS AF: 0.0260 AC: 89 AN: 3478

EpiCase AF: 0.0509

EpiControl AF: 0.0492

ClinVar

Significance: Affects

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

GLYCEROL QUANTITATIVE TRAIT LOCUS Other:1

Jan 01, 2013

OMIM

Significance: Affects

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Benign	0.0027	T
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.93	.;D
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D
MetaRNN	Benign	0.0089	T;T
MetaSVM	Uncertain	-0.070	T
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-7.5	D;D
REVEL	Uncertain	0.58
Sift	Uncertain	0.0080	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.38
MPC		0.77
ClinPred		0.088	T
GERP RS		4.3
Varity_R		0.98
Mutation Taster		=77/23	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs62542743; hg19: chr9-33385241; COSMIC: COSV53029199; COSMIC: COSV53029199;