11-77590014-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173039.3(AQP11):​c.22C>T​(p.Arg8Trp) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R8G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: AQP11 NM_173039.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.541
• Publications: 1 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04168114).

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>T	p.Arg8Trp	missense	Exon 1 of 3	NP_766627.1	Q8NBQ7
	AQP11	NM_001363477.2		c.22C>T	p.Arg8Trp	missense	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>T	p.Arg8Trp	missense	Exon 1 of 3	ENSP00000318770.3	Q8NBQ7
	AQP11	ENST00000528638.1	TSL:1	n.290+334C>T		intron	N/A
	AQP11	ENST00000925651.1		c.22C>T	p.Arg8Trp	missense	Exon 1 of 3	ENSP00000595710.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000626 AC: 1 AN: 159648 AF XY: 0.0000113

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000518

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.38e-7 AC: 1 AN: 1355426 Hom.: 0 Cov.: 31 AF XY: 0.00000150 AC XY: 1 AN XY: 666038

African (AFR) AF: 0.00 AC: 0 AN: 29318

American (AMR) AF: 0.0000348 AC: 1 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

ExAC AF: 0.00000829 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	2.7
DANN	Benign	0.95
DEOGEN2	Benign	0.084	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.48	N
PhyloP100		-0.54
PrimateAI	Benign	0.32	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.039
Sift	Benign	0.049	D
Sift4G	Benign	0.13	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.39		Loss of disorder (P = 0.0028)
MVP		0.35
MPC		0.52
ClinPred		0.074	T
GERP RS		-1.7
PromoterAI		-0.027	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.063
gMVP		0.47
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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;