11-77590426-A-C

Position:

• chr11-77590426-A-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_173039.3(AQP11):​c.434A>C​(p.Gln145Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00576 in 1,614,070 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0043 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0059 (38 hom.)
• Consequence: AQP11 NM_173039.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.70

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006157875).
• BP6: Variant 11-77590426-A-C is Benign according to our data. Variant chr11-77590426-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2642190.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AQP11	NM_173039.3	c.434A>C	p.Gln145Pro	missense_variant	1/3	ENST00000313578.4	NP_766627.1
AQP11	NM_001363477.2	c.434A>C	p.Gln145Pro	missense_variant	1/2		NP_001350406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AQP11	ENST00000313578.4	c.434A>C	p.Gln145Pro	missense_variant	1/3	1	NM_173039.3	ENSP00000318770	P1
AQP11	ENST00000528638.1	n.291-103A>C		intron_variant, non_coding_transcript_variant		1
CLNS1A	ENST00000526761.5	c.*156-4967T>G		intron_variant, NMD_transcript_variant		3		ENSP00000475218

Frequencies

GnomAD3 genomes AF: 0.00433 AC: 659 AN: 152102 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00891

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00622

Gnomad OTH AF: 0.00670

GnomAD3 exomes AF: 0.00396 AC: 995 AN: 251436 Hom.: 6 AF XY: 0.00407 AC XY: 553 AN XY: 135920

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.00494

Gnomad ASJ exome AF: 0.00218

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00150

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.00613

Gnomad OTH exome AF: 0.00538

GnomAD4 exome AF: 0.00591 AC: 8642 AN: 1461850 Hom.: 38 Cov.: 33 AF XY: 0.00582 AC XY: 4230 AN XY: 727238

Gnomad4 AFR exome AF: 0.00119

Gnomad4 AMR exome AF: 0.00530

Gnomad4 ASJ exome AF: 0.00253

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00137

Gnomad4 FIN exome AF: 0.000337

Gnomad4 NFE exome AF: 0.00696

Gnomad4 OTH exome AF: 0.00621

GnomAD4 genome AF: 0.00432 AC: 658 AN: 152220 Hom.: 3 Cov.: 32 AF XY: 0.00414 AC XY: 308 AN XY: 74418

Gnomad4 AFR AF: 0.00173

Gnomad4 AMR AF: 0.00889

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.00622

Gnomad4 OTH AF: 0.00663

Alfa AF: 0.00515 Hom.: 4

Bravo AF: 0.00461

TwinsUK AF: 0.00647 AC: 24

ALSPAC AF: 0.00545 AC: 21

ESP6500AA AF: 0.00205 AC: 9

ESP6500EA AF: 0.00524 AC: 45

ExAC AF: 0.00369 AC: 448

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00883

EpiControl AF: 0.00688

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

AQP11: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	15
DANN	Benign	0.87
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.0062	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.26
Sift	Benign	0.20	T
Sift4G	Benign	0.15	T
Polyphen		0.11	B
Vest4		0.21
MVP		0.77
MPC		0.72
ClinPred		0.0030	T
GERP RS		1.8
Varity_R		0.27
gMVP		0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs145893530; hg19: chr11-77301471; COSMIC: COSV99047011;