9-33385741-AA-GT

Variant names:

• chr9-33385741-AA-GT
• NM_001170.3:c.650_651delTTinsAC
• AQP7 p.Leu217His

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001170.3(AQP7):​c.650_651delTTinsAC​(p.Leu217His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AQP7 NM_001170.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.32
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.650_651delTTinsAC	p.Leu217His	missense	N/A	NP_001161.1	O14520-1
	AQP7	NM_001376191.1		c.650_651delTTinsAC	p.Leu217His	missense	N/A	NP_001363120.1	O14520-1
	AQP7	NM_001376192.1		c.650_651delTTinsAC	p.Leu217His	missense	N/A	NP_001363121.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP7	ENST00000297988.6	TSL:1 MANE Select	c.650_651delTTinsAC	p.Leu217His	missense	N/A	ENSP00000297988.1	O14520-1
	AQP7	ENST00000377425.8	TSL:1	c.479_480delTTinsAC	p.Leu160His	missense	N/A	ENSP00000396111.2	Q6P5T0
	AQP7	ENST00000537089.5	TSL:1	n.*370_*371delTTinsAC		non_coding_transcript_exon	Exon 6 of 6	ENSP00000441619.2	A0A096LNU3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.3

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr9-33385739;