chr9-33385773-C-T

Variant names:

• chr9-33385773-C-T
• rs117663392
• NM_001170.3:c.619G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 3P and 6B. PM2 PP3 BP4_Strong BP6_Moderate

The NM_001170.3(AQP7):​c.619G>A​(p.Gly207Ser) variant causes a missense change involving the alteration of a 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 Benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AQP7 NM_001170.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.90
• Publications: 13 publications found

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Multiple lines of computational evidence support a deleterious effect 4: BayesDel_addAF, FATHMM_MKL, phyloP100way_vertebrate, PROVEAN [when MetaRNN, MutationTaster was below the threshold]
• BP4: Computational evidence support a benign effect (MetaRNN=0.010802567).
• BP6: Variant 9-33385773-C-T is Benign according to our data. Variant chr9-33385773-C-T is described in ClinVar as Benign. ClinVar VariationId is 402387.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170.3. 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
	AQP7	NM_001170.3	MANE Select	c.619G>A	p.Gly207Ser	missense	Exon 7 of 8	NP_001161.1
	AQP7	NM_001376191.1		c.619G>A	p.Gly207Ser	missense	Exon 8 of 9	NP_001363120.1
	AQP7	NM_001376192.1		c.619G>A	p.Gly207Ser	missense	Exon 7 of 8	NP_001363121.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP7	ENST00000297988.6	TSL:1 MANE Select	c.619G>A	p.Gly207Ser	missense	Exon 7 of 8	ENSP00000297988.1
	AQP7	ENST00000377425.8	TSL:1	c.448G>A	p.Gly150Ser	missense	Exon 6 of 7	ENSP00000396111.2
	AQP7	ENST00000537089.5	TSL:1	n.*339G>A		non_coding_transcript_exon	Exon 6 of 6	ENSP00000441619.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00422 AC: 938 AN: 222256 AF XY: 0.00305

Gnomad AFR exome AF: 0.00560

Gnomad AMR exome AF: 0.000716

Gnomad ASJ exome AF: 0.00220

Gnomad EAS exome AF: 0.00138

Gnomad FIN exome AF: 0.00963

Gnomad NFE exome AF: 0.00611

Gnomad OTH exome AF: 0.00336

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.0139 Hom.: 0

ExAC AF: 0.0480 AC: 5824

ClinVar

ClinVar submissions as Germline

Significance: Benign

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	Uncertain	0.44
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.72	D
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0093	T
MetaSVM	Benign	-0.72	T
PhyloP100		7.9
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.52
Sift	Benign	0.038	D
Sift4G	Uncertain	0.041	D
Polyphen		0.30	B
Vest4		0.34
MPC		0.44
ClinPred		0.033	T
GERP RS		5.0
Varity_R		0.85
Mutation Taster		=14/86	disease causing

Splicing

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

Other links and lift over

dbSNP: rs117663392; hg19: chr9-33385771; COSMIC: COSV53004809; COSMIC: COSV53004809;