11-77590014-C-A

Variant names:

• chr11-77590014-C-A
• rs756558067
• NM_173039.3:c.22C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_173039.3(AQP11):​c.22C>A​(p.Arg8Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000738 in 1,355,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: AQP11 NM_173039.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.541
• Publications: 0 publications found

Genes affected

AQP11 (HGNC:19940): (aquaporin 11) Enables glycerol channel activity and water channel activity. Involved in several processes, including glycerol transport; hydrogen peroxide transmembrane transport; and protein homooligomerization. Located in cell surface; endoplasmic reticulum; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CLNS1A (HGNC:2080): (chloride nucleotide-sensitive channel 1A) This gene encodes a protein that functions in multiple regulatory pathways. The encoded protein complexes with numerous cytosolic proteins and performs diverse functions including regulation of small nuclear ribonucleoprotein biosynthesis, platelet activation and cytoskeletal organization. The protein is also found associated with the plasma membrane where it functions as a chloride current regulator. Pseudogenes of this gene are found on chromosomes 1, 4 and 6. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=-0.541 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173039.3. 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
	AQP11	NM_173039.3	MANE Select	c.22C>A	p.Arg8Arg	synonymous	Exon 1 of 3	NP_766627.1	Q8NBQ7
	AQP11	NM_001363477.2		c.22C>A	p.Arg8Arg	synonymous	Exon 1 of 2	NP_001350406.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP11	ENST00000313578.4	TSL:1 MANE Select	c.22C>A	p.Arg8Arg	synonymous	Exon 1 of 3	ENSP00000318770.3	Q8NBQ7
	AQP11	ENST00000528638.1	TSL:1	n.290+334C>A		intron	N/A
	AQP11	ENST00000925651.1		c.22C>A	p.Arg8Arg	synonymous	Exon 1 of 3	ENSP00000595710.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.38e-7 AC: 1 AN: 1355426 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 666038

African (AFR) AF: 0.0000341 AC: 1 AN: 29318

American (AMR) AF: 0.00 AC: 0 AN: 28700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20752

East Asian (EAS) AF: 0.00 AC: 0 AN: 36218

South Asian (SAS) AF: 0.00 AC: 0 AN: 72506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4944

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1064786

Other (OTH) AF: 0.00 AC: 0 AN: 55780

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	4.1
DANN	Benign	0.82
PhyloP100		-0.54
PromoterAI		-0.073	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs756558067; hg19: chr11-77301059;