9-33385752-C-T

Variant names:

• chr9-33385752-C-T
• rs114484742
• NM_001170.3:c.640G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001170.3(AQP7):​c.640G>A​(p.Gly214Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00011 in 1,613,676 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (1 hom.)
• Consequence: AQP7 NM_001170.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.05

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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008821577).
• BP6: Variant 9-33385752-C-T is Benign according to our data. Variant chr9-33385752-C-T is described in ClinVar as [Benign]. Clinvar id is 402386.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP7	NM_001170.3	c.640G>A	p.Gly214Arg	missense_variant	Exon 7 of 8	ENST00000297988.6	NP_001161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP7	ENST00000297988.6	c.640G>A	p.Gly214Arg	missense_variant	Exon 7 of 8	1	NM_001170.3	ENSP00000297988.1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00533 AC: 1170 AN: 219700 AF XY: 0.00331

Gnomad AFR exome AF: 0.0251

Gnomad AMR exome AF: 0.000238

Gnomad ASJ exome AF: 0.00411

Gnomad EAS exome AF: 0.000805

Gnomad FIN exome AF: 0.00643

Gnomad NFE exome AF: 0.00649

Gnomad OTH exome AF: 0.00416

GnomAD4 exome AF: 0.000112 AC: 163 AN: 1461484 Hom.: 1 Cov.: 33 AF XY: 0.0000949 AC XY: 69 AN XY: 727036

Gnomad4 AFR exome AF: 0.000120 AC: 4 AN: 33462

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 44724

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26136

Gnomad4 EAS exome AF: 0.0000504 AC: 2 AN: 39700

Gnomad4 SAS exome AF: 0.0000928 AC: 8 AN: 86234

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53404

Gnomad4 NFE exome AF: 0.000130 AC: 145 AN: 1111998

Gnomad4 Remaining exome AF: 0.0000663 AC: 4 AN: 60352

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152192 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74348

Gnomad4 AFR AF: 0.000121 AC: 0.000120674 AN: 0.000120674

Gnomad4 AMR AF: 0.000196 AC: 0.000196258 AN: 0.000196258

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000882 AC: 0.0000881808 AN: 0.0000881808

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.320 Hom.: 6594

Bravo AF: 0.0000567

ExAC AF: 0.0608 AC: 7384

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.78	.;D;D;.;.;D;.
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.78	T;D;T;D;T;T;D
MetaRNN	Benign	0.0088	T;T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-6.6	D;D;D;D;D;.;D
REVEL	Uncertain	0.33
Sift	Benign	0.059	T;D;T;D;D;.;D
Sift4G	Pathogenic	0.0010	D;D;D;.;D;D;D
Polyphen		0.26, 0.39, 0.76, 0.38	.;B;B;.;P;B;.
Vest4		0.33
MutPred		0.88		.;.;Loss of glycosylation at S216 (P = 0.098);.;.;Loss of glycosylation at S216 (P = 0.098);.;
MPC		0.55
ClinPred		0.044	T
GERP RS		4.9
Varity_R		0.97
Mutation Taster		=22/78	disease causing

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs114484742; hg19: chr9-33385750; COSMIC: COSV53003053; COSMIC: COSV53003053;