chr11-77590448-C-G

Variant names:

• chr11-77590448-C-G
• rs1442404559
• NM_173039.3:c.456C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173039.3(AQP11):​c.456C>G​(p.Ser152Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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 Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AQP11 NM_173039.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.333
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22310138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP11	NM_173039.3	c.456C>G	p.Ser152Arg	missense_variant	Exon 1 of 3	ENST00000313578.4	NP_766627.1
AQP11	NM_001363477.2	c.456C>G	p.Ser152Arg	missense_variant	Exon 1 of 2		NP_001350406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP11	ENST00000313578.4	c.456C>G	p.Ser152Arg	missense_variant	Exon 1 of 3	1	NM_173039.3	ENSP00000318770.3
AQP11	ENST00000528638.1	n.291-81C>G		intron_variant	Intron 1 of 3	1
CLNS1A	ENST00000526761.5	n.*156-4989G>C		intron_variant	Intron 3 of 5	3		ENSP00000475218.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Benign	0.93
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.66	T
M_CAP	Uncertain	0.092	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.33
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.37
Sift	Benign	0.10	T
Sift4G	Benign	0.60	T
Polyphen		0.66	P
Vest4		0.28
MutPred		0.56		Gain of methylation at S152 (P = 0.0184);
MVP		0.86
MPC		1.1
ClinPred		0.60	D
GERP RS		3.3
PromoterAI		0.0038	Neutral
Varity_R		0.11
gMVP		0.69
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1442404559; hg19: chr11-77301493;